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Measles, Mumps, and Rubella -- Vaccine Use and Strategies for
Elimination of Measles, Rubella, and Congenital Rubella Syndrome
and Control of Mumps: Recommendations of the Advisory Committee on
Immunization Practices (ACIP)

Article

SUMMARY

These revised recommendations of the Advisory Committee on
Immunization Practices (ACIP) on measles, mumps, and rubella
prevention supersede recommendations published in 1989 and 1990.
This statement summarizes the goals and current strategies for
measles, rubella, and congenital rubella syndrome (CRS)
elimination and for mumps reduction in the United States. Changes
from previous recommendations include

Emphasis on the use of combined MMR vaccine for most
indications;

A change in the recommended age for routine vaccination to 12-15
months for the first dose of MMR, and to 4-6 years for the
second dose of MMR;

A recommendation that all states take immediate steps to
implement a two dose MMR requirement for school entry and any
additional measures needed to ensure that all school-aged children
are vaccinated with two doses of MMR by 2001;

A clarification of the role of serologic screening to determine
immunity;

A change in the criteria for determining acceptable evidence of
rubella immunity;

A recommendation that all persons who work in health-care
facilities have acceptable evidence of measles and rubella
immunity;

Changes in the recommended interval between administration of
immune globulin and measles vaccination; and

Updated information on adverse events and contraindications,
particularly for persons with severe HIV infection, persons with
a history of egg allergy or gelatin allergy, persons with a
history of thrombocytopenia, and persons receiving steroid
therapy.

INTRODUCTION

Since monovalent vaccines containing measles, rubella, and
mumps vaccine viruses -- and subsequently combined
measles-mumps-rubella (MMR) vaccine -- were licensed, the numbers of
reported cases of measles, mumps, rubella, and congenital rubella
syndrome (CRS) have decreased by more than 99%. In 1993, the
Childhood Immunization Initiative established goals of eliminating
indigenous transmission of measles and rubella in the United
States by 1996. Subsequently, the goals of the initiative were
extended to include reducing the number of reported mumps cases to
less than or equal to 1600 by 1996. U.S. Public Health Service
year 2000 objectives include eliminating measles, rubella, and
congenital rubella syndrome, and reducing mumps incidence to less
than 500 reported cases per year. Since 1995, fewer cases of
measles, rubella, and mumps have been reported than at any time
since nationwide disease reporting began, and elimination of
indigenous transmission appears feasible. These recommendations
are intended to hasten the achievement of these disease
elimination goals.
Measles
Clinical Characteristics

The incubation period of measles (rubeola) averages 10-12
days from exposure to prodrome and 14 days from exposure to rash
(range: 7-18 days). The disease can be severe and is most
frequently complicated by diarrhea, middle ear infection, or
bronchopneumonia. Encephalitis occurs in approximately one of
every 1,000 reported cases; survivors of this complication often
have permanent brain damage and mental retardation. Death occurs
in 1-2 of every 1,000 reported measles cases in the United States.
The risk for death from measles or its complications is greater
for infants, young children, and adults than for older children
and adolescents. The most common causes of death are pneumonia and
acute encephalitis. In developing countries, measles is often more
severe and the case-fatality rate can be as high as 25%.

Subacute sclerosing panencephalitis (SSPE) is a rare
degenerative disease of the central nervous system associated with
measles virus. Signs and symptoms of the disease appear years
after measles infection. Widespread use of measles vaccine has
essentially eliminated SSPE from the United States (1).

Measles illness during pregnancy leads to increased rates of
premature labor, spontaneous abortion, and low birth weight among
affected infants (2-5). Birth defects, with no definable pattern
of malformation, have been reported among infants born to women
infected with measles during pregnancy, but measles infection has
not been confirmed as the cause of the malformations.

Measles can be severe and prolonged among immunocompromised
persons, particularly those who have certain leukemias, lymphomas,
or human immunodeficiency virus (HIV) infection. Among these
persons, measles may occur without the typical rash and a patient
may shed measles virus for several weeks after the acute illness
(6,7).
Measles Elimination

Before measles vaccine was licensed in 1963, an average of
400,000 measles cases were reported each year in the United States
(8). However, because virtually all children acquired measles, the
number of cases probably approached 3.5 million per year (i.e., an
entire birth cohort).

Since measles vaccine became available, professional and
voluntary medical and public health organizations have
collaborated in vaccination programs that have reduced the
reported incidence of measles by greater than 99%. During the late
1960s and early 1970s, the number of reported cases decreased to
approximately 22,000-75,000 cases per year. Although measles
incidence decreased substantially in all age groups, the greatest
decrease occurred among children aged less than 10 years. A less
marked decrease also occurred among older children.

During 1978, the Department of Health, Education, and Welfare
(DHEW) initiated a Measles Elimination Program with the goal of
eliminating indigenous measles from the United States by October
1, 1982. The three components of this program were a) maintenance
of high levels of immunity with a single dose of measles vaccine,
b) enhanced surveillance of disease, and c) aggressive outbreak
control. As a result of this program, the number of cases reported
annually decreased from 26,871 during 1978 to 1,497 during 1983.
However, an average of 3,750 cases was reported each year during
1984-1988; 58% of these cases occurred among children aged greater
than or equal to 10 years, most of whom had received only one dose
of measles vaccine (9). Recurrent measles outbreaks among
vaccinated school-aged children prompted both the Advisory
Committee on Immunization Practices (ACIP) and the American
Academy of Pediatrics (AAP) in 1989 to recommend that all children
receive two doses of measles-containing vaccine, preferably as
MMR. Although administration of the second dose was originally
recommended either at entry to primary school (ACIP) or middle/
secondary school (AAP), ACIP, the AAP, and the American Academy of
Family Physicians (AAFP) now recommend that a child receive the
second dose before school entry, rather than delaying it until the
child is aged 11-12 years.

During 1989-1991, a major resurgence of measles occurred in
the United States. More than 55,000 cases and greater than 120
measles-related deaths were reported. The resurgence was
characterized by an increasing proportion of cases among
unvaccinated preschool-aged children, particularly those resident
in urban areas (10-12).

Multiple barriers to timely vaccination of preschool-aged
children were identified during investigation of the 1989-1991
measles resurgence. Efforts to increase vaccination coverage among
preschool-aged children emphasized vaccination as close to the
recommended age as possible. These efforts, coupled with ongoing
implementation of the two-dose MMR recommendation, reduced
reported measles cases from 2,237 in 1992 to 312 in 1993 (9).
Although 963 measles cases were reported in 1994, measles
incidence again declined in 1995, when 309 cases were reported
(13). In 1996, 508 cases were reported, of which 65 were
classified as international importations (14).

In 1993, the Childhood Immunization Initiative called for the
elimination from the United States by 1996 of indigenous
transmission of six childhood diseases, including rubella,
congenital rubella syndrome (CRS), and measles (10). In September
1994, the Pan American Health Organization (PAHO) adopted a
similar goal of eliminating measles throughout the Americas by
2000 (15). Both epidemiologic and laboratory evidence suggest that
the transmission of indigenous measles was interrupted in the
United States for the first time during 1993 (16,17).

However, even after indigenous measles transmission has been
eliminated, measles cases caused by the importation of the virus
from other countries will continue to occur. Sustaining measles
elimination will require continuing efforts. Enhanced surveillance
for measles must be maintained and disease control activities must
be undertaken immediately when suspected cases of measles are
reported. The major challenges to sustaining the elimination of
measles from the United States are a) continuing to vaccinate all
children aged 12-15 months with a first dose of MMR, b) ensuring
that all school-aged children receive a second dose of MMR
vaccine, and c) working with other countries to set and achieve
national measles elimination goals.
Rubella And Congenital Rubella Syndrome (CRS)
Clinical Characteristics

Rubella is an exanthematous illness characterized by
nonspecific signs and symptoms including transient erythematous
and sometimes pruritic rash, postauricular or suboccipital
lymphadenopathy, arthralgia, and low-grade fever. Clinically
similar exanthematous illnesses are caused by parvovirus,
adenoviruses, and enteroviruses. Moreover, 25%-50% of rubella
infections are subclinical. The incubation period ranges from 12
to 23 days. Before rubella vaccine was available, the disease was
common among children and young adults.

Among adults infected with rubella, transient polyarthralgia
or polyarthritis occur frequently. These manifestations are
particularly common among women (18). Central nervous system
complications (i.e., encephalitis) occur at a ratio of 1 per 6,000
cases and are more likely to affect adults. Thrombocytopenia
occurs at a ratio of 1 per 3,000 cases and is more likely to
affect children.

The most important consequences of rubella are the
miscarriages, stillbirths, fetal anomalies, and therapeutic
abortions that result when rubella infection occurs during early
pregnancy, especially during the first trimester. An estimated
20,000 cases of CRS occurred during 1964-1965 during the last U.S.
rubella epidemic before rubella vaccine became available.

Infants who are moderately or severely affected by CRS are
readily recognizable at birth, but mild CRS (e.g., slight cardiac
involvement or deafness) may be detected months or years after
birth, or not at all. Although CRS has been estimated to occur
among 20%-25% of infants born to women who acquire rubella during
the first 20 weeks of pregnancy, this figure may underestimate the
risk for fetal infection and birth defects. When infants born to
mothers who were infected during the first 8 weeks of gestation
were followed for 4 years, 85% were found to be affected (19). The
risk for any defect decreases to approximately 52% for infections
that occur during the ninth to twelfth weeks of gestation.
Infection after the twentieth week of gestation rarely causes
defects. Inapparent (subclinical) maternal rubella infection can
also cause congenital malformations. Fetal infection without
clinical signs of CRS can occur during any stage of pregnancy.
Rubella Elimination

Before rubella vaccine was licensed during 1969, rubella
incidence was greatest among preschool and elementary school
children. Therefore, vaccination campaigns initially targeted
children in kindergarten and the early grades of elementary
school, with the aim of interrupting circulation of the virus and
eliminating the risk for exposure among susceptible pregnant
women. The risks associated with administering a potentially
teratogenic live virus vaccine to young women of childbearing age
were not known. During 1969-1976, reported rubella cases decreased
from 57,600 to 12,400. However, during 1975-1977, 62% of reported
rubella cases occurred among persons aged greater than 15 years
compared with 23% of cases occurring during 1966-1968, and
serologic studies suggested that 10%-15% of adults remained
susceptible to rubella (20).

The number of CRS cases reported nationwide decreased by 69%
from 69 in 1970 to 22 in 1976. Rubella outbreaks continued to
occur among older adolescents and young adults (e.g, in military
camps, high schools, colleges, and universities). In 1977, ACIP
modified its recommendations to include the vaccination of
susceptible postpubertal girls and women. During the same year,
the DHEW undertook the National Childhood Immunization Initiative,
which sought to immunize greater than 90% of the nation's children
against all vaccine-preventable diseases. Enforcement of
requirements for vaccination before school entry was part of the
initiative. The number of reported rubella and CRS cases decreased
after these programs were implemented, from 20,395 rubella cases
and 29 CRS cases in 1977 to 752 rubella cases and 2 CRS cases in
1984. In 1988, 225 cases of rubella were reported in the United
States, the fewest since national reporting began.

However, because of outbreaks among unvaccinated adults
(e.g., in prisons, colleges, and workplaces), greater than 1000
rubella cases were reported in 1990 and again in 1991. The largest
outbreak and the greatest number of CRS cases occurred among
children and adults in religious communities that do not accept
vaccination. Since 1992, reported indigenous rubella and CRS have
continued to occur at a low but relatively constant endemic level
with an annual average of less than 200 rubella cases (128 cases
in 1995 and 213 cases in 1996). Four confirmed CRS cases occurred
in 1995 and 2 in 1996. However, in the United States, surveillance
for CRS relies on a passive system. Consequently, the reported
annual totals of CRS are regarded as minimum figures, representing
an estimated 40%-70% of all cases (21,22).

During 1992-1997, 65% of reported cases of rubella occurred
among persons aged greater than or equal to 20 years. In addition,
recent evidence suggests that the risk for both rubella and CRS is
increased among persons of Hispanic ethnicity, particularly those
born outside the United States. Outbreaks of rubella in California
(1990-1991), Massachusetts (1993-1994), Connecticut (1995), and
North Carolina (1996 and 1997) have occurred primarily among
persons of Hispanic origin. During 1985-1995, the ethnicity of a
total of 89 children with laboratory-confirmed or clinically
compatible cases of CRS was known; 35 (39%) were of Hispanic
origin (23-27).

Recent data indicate that the rate of rubella susceptibility
and risk for rubella infection are highest among young adults.
During 1992-94, approximately 8% of persons aged 15-29 years were
estimated to lack serologic evidence of immunity to rubella (CDC,
unpublished data). Data from two recent studies indicate that
vaccine-induced rubella antibody levels among adolescents may have
decreased during the 9-14 years that had elapsed since they were
initially vaccinated. However, recent rubella surveillance data do
not indicate that rubella and CRS are increasing among vaccinated
persons (28) (CDC, unpublished data).

The primary objective of the rubella immunization program is
the prevention of CRS. The major components of the rubella and CRS
elimination strategy are achieving and maintaining high
immunization levels for children and adults, especially women of
childbearing age; conducting accurate surveillance for rubella and
CRS; and undertaking control measures promptly when a rubella
outbreak occurs. Since the late 1970s, this strategy has
effectively prevented major epidemics of rubella and CRS in the
United States.
Mumps
Clinical Characteristics

Persons in whom "classical" mumps develops have bilateral or
(less commonly) unilateral parotitis, with onset an average of 16-18
days after exposure. Parotitis may be preceded by fever,
headache, malaise, myalgia, and anorexia. Only 30%-40% of mumps
infections produce typical acute parotitis; 15%-20% of infections
are asymptomatic and up to 50% of infections are associated with
nonspecific or primarily respiratory symptoms (29,30). Inapparent
infection may be more common among adults than children; parotitis
occurs more commonly among children aged 2-9 years (30,31).
Serious complications of mumps infection can occur without
evidence of parotitis (29,32,33).

Most serious complications of mumps are more common among
adults than among children (29,34). Although orchitis may occur
among up to 38% of postpubertal men in whom mumps develops,
sterility is thought to occur only rarely (35).

Aseptic meningitis affects 4%-6% of persons with clinical
cases of mumps and typically is mild (29,36-38). However, mumps
meningoencephalitis can cause permanent sequelae, including
paralysis, seizures, cranial nerve palsies, aqueductal stenosis,
and hydrocephalus (39-41). In the prevaccine era, mumps was a
major cause of sensorineural deafness among children. Deafness may
be sudden in onset, bilateral, and permanent (42-44).

Among women in whom mumps develops during the first trimester
of pregnancy, an increased risk for fetal death has been observed
(45). However, mumps infection during pregnancy is not associated
with congenital malformations (46).
Mumps Control

In the United States, the reported incidence of mumps
decreased steadily after the introduction of live mumps vaccine in
1967 and the recommendation for its routine use in 1977. In 1995,
906 cases were reported, representing a 99% decrease from the
185,691 cases reported in 1968. The enactment and enforcement of
state vaccination laws requiring that students be vaccinated
before school entry has contributed more to reducing mumps
incidence than any other measure (47). During the 1980s and early
1990s, mumps incidence was lowest in states where comprehensive
vaccination laws were enforced. States where vaccination laws were
less comprehensive reported intermediate mumps incidence, and the
highest incidence was reported in states did not have such laws
(47-51).

Mumps incidence is now very low in all areas of the United
States. The substantial reduction in mumps incidence during the
past few years may reflect the change in the recommendations for
use of MMR vaccine. The implementation of the two-dose MMR
vaccination schedule likely decreased mumps incidence further by
immunizing children among whom the first dose of mumps antigen did
not elicit an immune response (52,53). The principal strategy to
prevent mumps is to achieve and maintain high immunization levels
by routinely vaccinating all children with two doses of MMR.
VACCINE PREPARATIONS

Since 1963, when both inactivated and live attenuated
(Edmonston B strain) vaccines were licensed, the type of measles
vaccine used in the United States has changed several times.
Distribution of the inactivated and live Edmonston B vaccines
ceased after 1967 and 1975, respectively. Distribution in the
United States of a live, further attenuated vaccine (Schwarz
strain) first introduced in 1965 has also ceased. A live, further
attenuated preparation of the Enders-Edmonston virus strain that
is grown in chick embryo fibroblast cell culture, licensed in
1968, is the only measles virus vaccine now available in the
United States. This further attenuated vaccine (formerly called
"Moraten") causes fewer adverse reactions than the Edmonston B
vaccine.

Measles vaccine produces an inapparent or mild,
noncommunicable infection. Measles antibodies develop among
approximately 95% of children vaccinated at age 12 months and 98%
of children vaccinated at age 15 months (CDC, unpublished data).
Studies indicate that, if the first dose is administered no
earlier than the first birthday, greater than 99% of persons who
receive two doses of measles vaccine develop serologic evidence of
measles immunity (54)(CDC, unpublished data). Although vaccination
produces lower antibody levels than natural disease, both
serologic and epidemiologic evidence indicate that the vaccine
induces long-term -- probably lifelong -- immunity, in most persons
(55). Most vaccinated persons who appear to lose antibody show an
anamnestic immune response upon revaccination, indicating that
they are probably still immune (56). Although revaccination
elicits increased antibody levels in some persons, these increased
levels may not be sustained (57). Findings of some studies
indicate that immunity can wane after successful vaccination
(secondary vaccine failure), but this phenomenon appears to occur
rarely and to have little effect on measles transmission and the
occurrence of outbreaks (55,58,59).
Rubella Component

The live rubella virus vaccine currently distributed in the
United States is prepared in human diploid cell culture. This
vaccine, containing virus strain RA 27/3, was licensed in the
United States in January, 1979 and replaced previous rubella
vaccines (e.g., HPV-77 and Cendehill) because it induced an
increased and more persistent antibody response and was associated
with fewer adverse events.

In clinical trials, greater than or equal to 95% of
susceptible persons aged greater than or equal to 12 months who
received a single dose of strain RA 27/3 rubella vaccine developed
serologic evidence of immunity (60-62). Clinical efficacy and
challenge studies indicate that greater than 90% of vaccinated
persons have protection against both clinical rubella and viremia
for at least 15 years (63-66). Follow-up studies indicate that one
dose of vaccine confers long-term -- probably lifelong -- protection
(67). Although antibody titers induced by the vaccine are
generally lower than those stimulated by rubella infection,
vaccine-induced immunity protects, in nearly all instances,
against both clinical illness and viremia after natural exposure
(68,69). In studies that attempted artificial reinfection of
persons who received RA 27/3 vaccine, resistance to reinfection
was similar to the resistance that follows natural infection (70).
However, several reports indicate that viremic reinfection
following exposure may occur among vaccinated persons who have low
levels of detectable antibody (64). The frequency and consequences
of this phenomenon are unknown but it is believed to be uncommon.
Clinical reinfection and fetal infection among persons who
developed immunity as a consequence of infection with wild virus
have been documented, but are apparently rare (71). Rarely,
clinical reinfection and fetal infection have been reported among
women with vaccine-induced immunity. Rare cases of CRS have
occurred among infants born to mothers who had documented
serologic evidence of rubella immunity before they became
pregnant.
Mumps Component

The only mumps vaccine now available in the United States is
a live virus vaccine (Jeryl-Lynn strain) that is prepared in
chick-embryo cell culture. The vaccine produces a subclinical,
noncommunicable infection with very few side effects.

More than 97% of persons who are susceptible to mumps develop
measurable antibody following vaccination and, in controlled
clinical trials, one dose of vaccine was approximately 95%
efficacious in preventing mumps disease (72-74). However, field
studies have documented lower estimates of vaccine efficacy,
ranging from 75% to 95% (47,75). Antibody levels induced by the
vaccine are lower than antibody levels resulting from natural
infection (72,76,77). The duration of vaccine-induced immunity is
unknown, but serologic and epidemiologic data collected during 30
years of live vaccine use indicate both the persistence of
antibody and continuing protection against infection (33,78,79).
Vaccine Shipment and Storage

Administration of improperly stored vaccine may fail to
provide protection against disease from measles, rubella, and/or
mumps. These live virus vaccines are supplied in lyophilized form
and should be stored at 2-8 C (35.6-46.4 F) or colder. They must
be shipped at 10 C (50 F) or colder and may be shipped on dry ice.
The vaccines must be protected from light, which may inactivate
the vaccine viruses. Reconstituted vaccine also must be protected
from light, must be stored at 2-8 C (35.6-46.4 F), and must not be
frozen. Reconstituted vaccine must be discarded if not used within
8 hours.
VACCINE USAGE

Two doses of MMR vaccine separated by at least 1 month (i.e.,
a minimum of 28 days) and administered on or after the first
birthday are recommended for all children and for certain
high-risk groups of adolescents and adults. The recommended 1
month interval between successive doses of MMR or other
measles-containing vaccine is based on the principle that live
virus vaccines not administered at the same time should be
separated by at least 1 month (80).

MMR is the vaccine of choice when protection against any of
these three diseases is required on or after the first birthday,
unless any of its component vaccines is contraindicated. The
purpose of the two-dose vaccination schedule is to produce
immunity in the small proportion of persons who fail to respond
immunologically to one or more of the components of the first
dose. Studies indicate that two doses of measles vaccine are
necessary to develop adequate population immunity to prevent
measles outbreaks among school-aged and older persons. Mumps can
occur in highly vaccinated populations; in these outbreaks,
substantial numbers of cases have occurred among persons who had
previously received a single dose of mumps-containing vaccine
(33,81). Although primary rubella vaccine failure rarely occurs,
the potential consequences of failure (i.e., CRS) are substantial.

Almost all persons who do not respond to the measles
component of the first dose of MMR vaccine will respond to the
second dose (82) (CDC, unpublished data). Few data regarding the
immune response to the rubella and mumps components of a second
dose of MMR vaccine are available, but most persons who do not
respond to the rubella or mumps components of the first dose would
be expected to respond to the second (82-84) (CDC, unpublished
data). The second dose is not generally considered a booster dose
because a primary immune response to the first dose provides
long-term protection. Although some persons who develop normal
antibody titers in response to a single dose of MMR vaccine will
develop higher antibody titers to the three component vaccines
when administered a second dose of vaccine, these increased
antibody levels typically do not persist (57).

Use of combined MMR vaccine for both measles doses and all
other indications should provide an additional safeguard against
primary vaccine failures and facilitate elimination of rubella and
CRS and continued reduction of mumps incidence. Data also indicate
that the favorable benefit/cost ratio for routine measles,
rubella, and mumps vaccination is even greater when the vaccines
are administered as combined MMR vaccine (85,86).
Dosage and Route of Administration

The lyophilized live MMR vaccine (and its component vaccines)
should be reconstituted and administered as recommended by the
manufacturer. All measles-, rubella-, or mumps-containing vaccines
available in the United States should be administered
subcutaneously in the recommended standard single-dose volume of
0.5 mL.
Simultaneous Administration of Vaccines

In general, simultaneous administration of the most widely
used live and inactivated vaccines does not impair antibody
responses or increase rates of adverse reactions (80). The
antibody responses of persons vaccinated with MMR are similar to
those of persons vaccinated with single-antigen measles, mumps,
and rubella vaccines at different sites or at different times.

ACIP encourages routine simultaneous administration of MMR,
diphtheria and tetanus toxoids and acellular pertussis (DTaP) or
diphtheria and tetanus toxoids and whole-cell pertussis (DTP)
vaccine, Haemophilus influenzae type b (Hib) vaccine, and oral
poliovirus vaccine (OPV) or inactivated poliovirus vaccine (IPV)
to children who are at the recommended age to receive these
vaccines. Antibody responses were equivalent and no clinically
significant increases in the frequency of adverse events occurred
when MMR vaccine, DTaP (or DTP), Hib vaccine, hepatitis B vaccine,
and IPV or OPV were administered either simultaneously at
different sites or at separate times (87). Likewise,
seroconversion rates, antibody levels, and frequencies of adverse
reactions were similar in two groups, one of which was
administered MMR and varicella vaccines simultaneously at separate
sites and the other of which received the vaccines 6 weeks apart
(88)(Merck Research Laboratories, unpublished data).

Live measles and yellow fever vaccines can be administered
simultaneously at separate anatomical sites in separate syringes
(89). Limited data also indicate that the immunogenicity and
safety of inactivated Japanese encephalitis vaccine are not
compromised by simultaneous administration with live measles
vaccine (90). Limited data exist concerning concurrent
administration of MMR vaccine and other vaccines that are often
recommended for international travelers (e.g., meningococcal
vaccine, typhoid vaccines). However, neither theoretical
considerations nor practical experience indicate that the
simultaneous administration at separate anatomic sites of MMR and
other live or inactivated vaccines will produce a diminished
immune response or increase the incidence of adverse events among
vaccinated persons.
DOCUMENTATION OF IMMUNITY

Only doses of vaccine for which written documentation of the
date of administration is presented should be considered valid.
Neither a self-reported dose nor a history of vaccination provided
by a parent is, by itself, considered adequate documentation. No
health-care worker should provide a vaccination record for a
patient unless that health-care worker has administered the
vaccine or has seen a record that documents vaccination. Persons
who may be immune to measles, mumps, or rubella but who lack
either adequate documentation of vaccination or other acceptable
evidence of immunity (Table 1) should be vaccinated. Vaccination
status and date of administration of all vaccinations should be
documented in the patient's permanent medical record.

Serologic screening for measles, rubella, or mumps immunity
generally is neither necessary nor recommended if a person has
other acceptable evidence of immunity to the disease (Table 1).
Serologic screening can be a barrier to vaccination. With the
exception of women who are known to be pregnant (see Women of
Childbearing Age), persons who lack acceptable evidence of
immunity generally should be vaccinated without serologic testing.
Serologic screening is appropriate only when persons identified as
susceptible are subsequently vaccinated in a timely manner.
Screening is most applicable when the return and vaccination of
those tested can be ensured (e.g., hiring of new health-care
workers). If these conditions are not met, serologic screening is
inappropriate (91). Likewise, during an outbreak of measles,
rubella, or mumps, serologic screening before vaccination
generally is not recommended because waiting for results,
contacting, and then vaccinating persons identified as susceptible
can impede the rapid vaccination needed to curb the outbreak.

Serologic screening for antibodies to measles, rubella, or
mumps alone will not identify persons who are susceptible to the
other diseases for which screening is not done. Post-vaccination
serologic testing to verify an immune response to MMR or its
component vaccines is not recommended.

The criteria for acceptable evidence of immunity to measles,
rubella, and mumps (Table 1) provide presumptive rather than
absolute evidence of immunity. Occasionally, a person who meets
the criteria for presumptive immunity can contract and transmit
disease. Specific criteria for documentation of immunity have been
established for certain persons (e.g., health-care workers,
international travelers, and students at post-high school
educational institutions) who are at increased risk for exposure
to measles, rubella, and mumps (Table 1). Criteria accepted as
evidence of immunity for the purpose of meeting school or college
entry requirements or other government regulations may vary among
state and local jurisdictions.
Measles

Persons generally can be presumed immune to measles (Table 1)
if they have documentation of adequate vaccination, laboratory
evidence of immunity to measles, documentation of
physician-diagnosed measles, or were born before 1957. Criteria
for adequate vaccination currently vary depending on state and
local vaccination policy because of differences in the way states
have implemented the two-dose measles vaccination schedule. All
states are strongly encouraged to take immediate steps to
implement the two-dose MMR vaccination schedule so that, by 2001,
adequate vaccination of children will be defined in all 50 states
as follows:

For preschool-aged children: documentation of at least one dose
of MMR vaccine administered on or after the first birthday.

For children in kindergarten through grade 12: documentation of
two doses of MMR vaccine separated by at least 28 days (i.e., 1
month), with the first dose administered no earlier than the first
birthday.

Doses of MMR and other measles-containing vaccines
administered before the first birthday should not be counted when
determining adequacy of measles vaccination.

When measles virus is introduced into a community, persons
who work in health-care facilities are at greater risk for
acquiring measles than the general population (92). Because
persons working in medical settings have been infected with and
have transmitted measles to patients and coworkers, rigorous
criteria for immunity among health-care workers have been
established. For persons born during or after 1957 who work in
health-care facilities, adequate vaccination consists of two doses
of MMR or other live measles-containing vaccine separated by at
least 28 days, with the first dose administered no earlier than
the first birthday (Table 1). In addition, although birth before
1957 is generally considered acceptable evidence of measles
immunity (Table 1), measles has occurred in some unvaccinated
persons born before 1957 who worked in health-care facilities.
Therefore, health-care facilities should consider recommending a
dose of MMR vaccine for unvaccinated workers born before 1957 who
lack a history of measles disease or laboratory evidence of
measles immunity (see Health-Care Facilities).

The previously described criteria apply only to routine
vaccination. During measles outbreaks, evidence of adequate
vaccination for school-aged children, adolescents, and adults born
during or after 1957 who are at risk for measles exposure and
infection consists of two doses of measles-containing vaccine
separated by at least 28 days, with the first dose administered no
earlier than the first birthday (see Measles Outbreak Control).
During outbreaks involving preschool-aged children, authorities
should consider extending this criterion to all children aged
greater than or equal to 12 months.

In the past, the most commonly used laboratory test for
assessing immunity to measles was the hemagglutination-inhibition
(HI) test but more sensitive assays (e.g., the enzyme immunoassay
{EIA} or enzyme-linked immunosorbent assay {ELISA}) are now used
in most laboratories. Persons who have measles-specific antibody
that is detectable by any serologic test are considered immune.
Persons with an "equivocal" test result should be considered
susceptible unless they have other evidence of measles immunity
(Table 1) or subsequent testing indicates they are immune. All new
cases of suspected measles should be confirmed by laboratory
testing (see Measles Case Investigation Laboratory Diagnosis).
Rubella

Persons generally can be presumed immune to rubella (Table 1)
if they have documentation of vaccination with at least one dose
of MMR or other live rubella-containing vaccine administered on or
after the first birthday, laboratory evidence of rubella immunity,
or were born before 1957 (except women who could become pregnant).
Birth before 1957 is not acceptable evidence of rubella immunity
for women who could become pregnant because it provides only
presumptive evidence of rubella immunity and does not guarantee
that a person is immune (see Women of Childbearing Age). Rubella
can occur among some unvaccinated persons born before 1957 and
congenital rubella and CRS can occur among the offspring of women
infected with rubella during pregnancy.

Persons who have an "equivocal" serologic test result should
be considered susceptible to rubella unless they have evidence of
adequate vaccination or a subsequent serologic test result
indicates rubella immunity. Although only one dose of
rubella-containing vaccine is required as acceptable evidence of
immunity to rubella, children should receive two doses of MMR
vaccine. The first dose is administered routinely when the child
is aged 12-15 months and the second before the child enters school
(i.e., at age 4-6 years)(see Routine Vaccination).

The clinical diagnosis of rubella is unreliable and should
not be considered in assessing immune status. Because many rash
illnesses may mimic rubella infection and many rubella infections
are unrecognized, the only reliable evidence of previous rubella
infection is the presence of serum rubella immunoglobulin G (IgG).
Laboratories that regularly perform antibody testing generally
provide the most reliable results because their reagents and
procedures are more likely to be strictly standardized (see
Rubella Case Investigation and Outbreak Control).

Postinfection immunity to rubella appears to be long-lasting
and is probably lifelong. However, as with other viral diseases,
re-exposure to natural rubella occasionally leads to reinfection
without clinical illness or detectable viremia. The risk for CRS
among infants born to women reinfected with rubella during
pregnancy is minimal (93,94). Although data from several studies
indicate that levels of vaccine-induced rubella antibodies may
decline with time, data from surveillance of rubella and CRS
suggest that waning immunity with increased susceptibility to
rubella disease does not occur (28)(CDC, unpublished data).

HI antibody testing was formerly the method most frequently
used to screen for rubella antibodies. However, the HI test has
been supplanted by other assays of equal or greater sensitivity.
EIAs are the most commonly used of these newer commercial assays,
but latex agglutination, immunofluorescence assay (IFA), passive
hemagglutination, hemolysis-in-gel, and virus neutralization tests
are also available.

Any antibody level above the standard positive cutoff value
of the assay with which it is measured can be considered evidence
of immunity, if the assay is licensed. When serum specimens from
adults who did not produce antibodies detectable by HI after
vaccination were examined with an equivalently specific but more
sensitive test, almost all had detectable antibody (95,96). A few
children who initially developed antibody detectable by HI
apparently "lost" this antibody during follow-up intervals of up
to 16 years (77,97,98). However, almost all had antibody
detectable by more sensitive tests. In several of these cases,
immunity was confirmed by documenting a booster response (i.e.,
absence of IgM antibody and a rapid rise in IgG antibody) after
revaccination (62,99).

Occasionally, persons with documented histories of rubella
vaccination have rubella serum IgG levels that are not clearly
positive by ELISA. Such persons can be administered a dose of MMR
vaccine and need not be retested for serologic evidence of rubella
immunity.
Mumps

Persons generally can be presumed immune to mumps (Table 1)
if they have documentation of vaccination with live mumps virus
vaccine on or after the first birthday, laboratory evidence of
mumps immunity, documentation of physician-diagnosed mumps, or
were born before 1957.

The demonstration of mumps IgG antibody by any commonly used
serologic assay is acceptable evidence of mumps immunity. Persons
who have an "equivocal" serologic test result should be considered
susceptible to mumps unless they have other evidence of mumps
immunity (Table 1) or subsequent testing indicates they are
immune. All new cases of suspected mumps should be confirmed by an
appropriate serologic assay (see Mumps Case Investigation,
Laboratory Diagnosis).

Live mumps vaccine was not used routinely before 1977. Before
the vaccine was introduced, the age-specific incidence of the
disease peaked among children aged 5-9 years. Therefore, most
persons born before 1957 are likely to have been infected
naturally between 1957 and 1977 and may be presumed immune, even
if they have not had clinically recognizable mumps disease.
However, birth before 1957 does not guarantee mumps immunity.
Therefore, during mumps outbreaks, MMR vaccination should be
considered for persons born before 1957 who may be exposed to
mumps and who may be susceptible. Laboratory testing for mumps
susceptibility before vaccination is not necessary.
ROUTINE VACCINATION
Preschool-Aged Children

Children should receive the first dose of MMR vaccine at age
12-15 months (i.e., on or after the first birthday). In areas
where risk for measles is high, initial vaccination with MMR
vaccine is recommended for all children as soon as possible upon
reaching the first birthday (i.e., at age 12 months). An area
where measles risk is high is defined as:

a county with a large inner city population,

a county where a recent measles outbreak has occurred among
unvaccinated preschool-aged children, or

a county in which more than five cases of measles have occurred
among preschool-aged children during each of the last 5 years.

These recommendations may be implemented for an entire county
or only within defined areas of a county. This strategy assumes
that the benefit of preventing measles cases among children aged
12-15 months outweighs the slightly reduced efficacy of the
vaccine when administered to children aged less than 15 months. In
addition, almost all children who do not respond immunologically
to the first dose of MMR vaccine will develop measles immunity
after receiving a second dose. HIV-infected children should
receive MMR vaccine at age 12 months, if not otherwise
contraindicated (see Special Considerations for Vaccination --
Persons Infected with Human Immunodeficiency Virus (HIV)).
School-Aged Children and Adolescents

The second dose of MMR vaccine is recommended when children
are aged 4-6 years (i.e., before a child enters kindergarten or
first grade). This recommended timing for the second dose of MMR
vaccine has been adopted jointly by ACIP, the American Academy of
Pediatrics (AAP), and the American Academy of Family Physicians
(AAFP). Evidence now indicates that a) the major benefit of
administering the second dose is a reduction in the proportion of
persons who remain susceptible because of primary vaccine failure,
b) waning immunity is not a major cause of vaccine failure and has
little influence on measles transmission, and c) revaccination of
children who have low levels of measles antibody produces only a
transient rise in antibody levels (55,57-59,100,101).

Because approximately 5% of children who receive only one
dose of MMR vaccine fail to develop immunity to measles, ACIP
recommends that all states implement a requirement that all
children entering school have received two doses of MMR vaccine
(with the first dose administered no earlier than the first
birthday) or have other evidence of immunity to measles, rubella,
and mumps (see Documentation of Immunity). In addition, to achieve
complete immunization of all school-aged children and hasten
progress toward measles elimination, states are strongly
encouraged to take immediate steps to ensure that, by 2001, all
children in grades kindergarten through 12 have received two doses
of MMR vaccine.

As part of comprehensive health services for all adolescents,
ACIP, AAP, and AAFP recommend a health maintenance visit at age
11-12 years. This visit should serve as an opportunity to evaluate
vaccination status and administer MMR vaccine to all persons who
have not received two doses at the recommended ages.

Children who do not have documentation of adequate
vaccination against measles, rubella, and mumps or other
acceptable evidence of immunity to these diseases (see
Documentation of Immunity) should be admitted to school only after
administration of the first dose of MMR vaccine. If required, the
second MMR dose should be administered as soon as possible, but no
sooner than 28 days after the first dose. Children who have
already received two doses of MMR vaccine at least 1 month apart,
with the first dose administered no earlier than the first
birthday, do not need an additional dose when they enter school.
Adults

Persons born in 1957 or later who are aged greater than or
equal to 18 years and who do not have a medical contraindication
should receive at least one dose of MMR vaccine unless they have
a) documentation of vaccination with at least one dose of
measles-, rubella-, and mumps-containing vaccine or b) other
acceptable evidence of immunity to these three diseases (Table 1).
Persons born before 1957 generally can be considered immune to
measles and mumps. In addition, persons born before 1957, except
women who could become pregnant, generally can be considered
immune to rubella.

MMR vaccine (one dose or two doses administered at least 28
days apart) may be administered to any person born before 1957 for
whom the vaccine is not contraindicated. Adults who may be at
increased risk for exposure to and transmission of measles, mumps,
and rubella should receive special consideration for vaccination.
These persons include international travelers, persons attending
colleges and other post-high school educational institutions, and
persons who work at health-care facilities. In addition, all women
of childbearing age should be considered susceptible to rubella
unless they have received at least one dose of MMR or other live
rubella virus vaccine on or after the first birthday or have
serologic evidence of immunity. Vaccination recommendations for
these high-risk groups follow.
Women of Childbearing Age

MMR vaccine should be offered to all women of childbearing
age (i.e., adolescent girls and premenopausal adult women) who do
not have acceptable evidence of rubella immunity whenever they
make contact with the health-care system. Opportunities to
vaccinate susceptible women include occasions when their children
undergo routine examinations or vaccinations. The continuing
occurrence of rubella among women of childbearing age indicates
the need to continue vaccination of susceptible adolescent and
adult women of childbearing age, and the absence of evidence of
vaccine teratogenicity indicates that the practice is safe (102).
Vaccination of susceptible women of childbearing age should

be part of routine general medical and gynecologic outpatient
care;

take place in all family-planning settings; and

be provided routinely before discharge from any hospital,
birthing center, or other medical facility, unless a specific
contraindication exists (see Precautions and Contraindications).

Outbreaks of rubella in the United States recently have
occurred among women of Hispanic ethnicity, many of whom were born
outside the fifty states. Efforts should be made to ensure that
all susceptible women of childbearing age, especially those who
grew up outside the fifty states in areas where routine rubella
vaccination may not occur, are vaccinated with MMR vaccine or have
other acceptable evidence of immunity (Table 1). Ascertainment of
rubella-immune status of women of childbearing age and the
availability of rubella vaccination should be components of the
health-care program in places where the risks for disease exposure
and transmission are substantial (e.g., day care facilities,
schools, colleges, jails, and prisons).
No evidence indicates that administration of
rubella-containing vaccine virus to a pregnant woman presents a
risk for her fetus, although such a risk cannot be excluded on
theoretical grounds. Therefore, women of childbearing age should
receive rubella-containing vaccines (i.e., rubella, MR, or MMR
vaccine) only if they state that they are not pregnant and only if
they are counseled not to become pregnant for 3 months after
vaccination. Because of the importance of protecting women of
childbearing age against rubella, reasonable practices in any
immunization program include a) asking women if they are pregnant,
b) not vaccinating women who state that they are pregnant, c)
explaining the potential risk for the fetus to women who state
that they are not pregnant, and d) counseling women who are
vaccinated not to become pregnant during the 3 months following
MMR vaccination.

Routine Vaccination of Women Who Are Not Pregnant. Women of
childbearing age who do not have documentation of rubella
vaccination or serologic evidence of rubella immunity should be
vaccinated with MMR, if they have no contraindications to the
vaccine. Birth before 1957 is not acceptable evidence of immunity
for women who could become pregnant (Table 1). The use of MMR
vaccine provides the potential additional benefit of protection
against measles and mumps. Serologic testing before vaccination is
not necessary and might present a barrier to timely vaccination.
Routine testing for rubella antibody during clinic visits for
routine health care, premarital evaluation, family planning, or
diagnosis and treatment of sexually transmitted diseases may
identify women who are not immune to rubella before they become
pregnant. Such routine serologic testing is not useful unless it
is linked to timely follow-up and vaccination of women who are
susceptible (103).

Prenatal Screening and Postpartum Vaccination. Prenatal serologic
screening of women who have acceptable evidence of rubella
immunity is generally not necessary, but is indicated for all
pregnant women who lack acceptable evidence of rubella immunity
(Table 1). Upon completion or termination of their pregnancies,
women who do not have serologic evidence of rubella immunity or
documentation of rubella vaccination should be vaccinated with MMR
before discharge from the hospital, birthing center, or abortion
clinic (104). They should be counseled to avoid conception for 3
months after vaccination. Postpartum rubella vaccination of all
women not known to be immune could prevent up to half of CRS cases
(105-108) (CDC, unpublished data).

Colleges and Other Post-High School Educational Institutions

Risks for transmission of measles, rubella, and mumps at
post-high school educational institutions can be high because
these institutions may bring together large concentrations of
persons susceptible to these diseases (109-113). Therefore,
colleges, universities, technical and vocational schools, and
other institutions for post-high school education should require
that all undergraduate and graduate students have received two
doses of MMR vaccine or have other acceptable evidence of measles,
rubella, and mumps immunity (Table 1) before enrollment.

College entry requirements for measles immunity substantially
reduce the risk for measles outbreaks on college campuses where
they are implemented and enforced (111). State requirements for
pre-enrollment vaccination ensure the best protection against
widespread measles transmission among students at college campuses
and other post-high school educational institutions. States are
strongly encouraged to adopt such regulations. Students who do not
have documentation of live measles, rubella, or mumps vaccination
or other acceptable evidence of immunity at the time of enrollment
(Table 1) should be admitted to classes only after receiving the
first dose of MMR vaccine. These students should be administered
a second dose of MMR vaccine 1 month (i.e., at least 28 days)
later. Students who have documentation of having received only one
dose of measles-containing vaccine on or after the first birthday
should receive a second dose of MMR before enrollment, provided at
least 1 month has elapsed since the previous dose. Students who
have a medical contraindication to receiving any of the components
of MMR vaccine should be given a letter of explanation to present
to the health officials of their educational institution.
Health-Care Facilities

When measles virus is introduced into a community, persons
who work in health-care facilities are at increased risk for
acquiring measles compared with the general population
(92,114,115). During 1985-1991, at least 795 measles cases (1.1%
of all reported cases) occurred among adult health-care workers.
Of these, 29% occurred among nurses, 15% among physicians, 11%
among persons in other health-care occupations (e.g., laboratory
and radiology technicians, etc.), 11% among clerks, 4% among
nursing assistants, and 4% among medical and nursing students
(115) (CDC, unpublished data). A general decline in measles
incidence occurred after 1991. However, 15 of the 75 measles
outbreaks reported during 1993-1996 involved transmission in a
medical facility, and a total of 36 measles cases (1.8% of all
reported cases) occurred among persons working in health-care
facilities (CDC, unpublished data). Although similar surveillance
data are not available for rubella, outbreaks have occurred in
health-care settings, and health-care workers have transmitted
rubella to patients (116) (CDC, unpublished data).

All persons who work in health-care facilities should be
immune to measles and rubella (Table 1). Because any health-care
worker (i.e., medical or nonmedical, paid or volunteer, full- or
part-time, student or nonstudent, with or without patient-care
responsibilities) who is not immune to measles and rubella can
contract and transmit these diseases, all health-care facilities
(i.e., inpatient and outpatient, private and public) should ensure
that those who work in their facilities are immune to measles and
rubella (Table 1) *.

Health-care workers have a responsibility to avoid
transmitting these diseases and thereby causing harm to patients.
Adequate vaccination for health-care workers born during or after
1957 consists of two doses of a live measles-containing vaccine
and at least one dose of a live rubella-containing vaccine (Table 1).
Health-care workers who need a second dose of
measles-containing vaccine should be revaccinated 1 month (at
least 28 days) after their first dose.

Although birth before 1957 is generally considered acceptable
evidence of measles and rubella immunity (Table 1), health-care
facilities should consider recommending a dose of MMR vaccine to
unvaccinated workers born before 1957 who do not have a history of
physician-diagnosed measles or laboratory evidence of measles
immunity AND laboratory evidence of rubella immunity.

Rubella vaccination or laboratory evidence of rubella
immunity is particularly important for female health-care workers
who could become pregnant, including those born before 1957. In
addition, during rubella outbreaks, health-care facilities should
strongly consider recommending a dose of MMR vaccine to
unvaccinated health-care workers born before 1957 who do not have
serologic evidence of immunity. Serologic surveys of hospital
workers indicate that 5%-9% of those born before 1957 do not have
detectable measles antibody (117,118) and about 6% do not have
detectable rubella antibody (119). In addition, during 1985-1992,
643 measles cases were reported among health-care workers whose
year of birth was known; 27% of these persons were born before
1957 (CDC, unpublished data). Comparable surveillance data are not
available for rubella.

Serologic screening need not be done before vaccinating for
measles and rubella unless the medical facility considers it
cost-effective (91,120,121). Serologic testing is appropriate only
if persons who are identified as susceptible are subsequently
vaccinated in a timely manner. Serologic screening ordinarily is
not necessary for persons who have documentation of appropriate
vaccination or other acceptable evidence of immunity (Table 1).
During outbreaks of measles or rubella, serologic screening before
vaccination is not generally recommended because rapid vaccination
is necessary to halt disease transmission.

Transmission of mumps has occurred in medical settings (122).
Therefore, immunity to mumps is highly desirable for all
health-care workers (Table 1). Adequate mumps vaccination for
health-care workers born during or after 1957 consists of one dose
of live mumps-containing vaccine.

MMR vaccine generally should be used whenever any of its
component vaccines is indicated. However, if the prospective
vaccinee has acceptable evidence of immunity to one or two of the
components of MMR vaccine (Table 1), a monovalent or bivalent
vaccine can be used.
International Travel

Measles, rubella, and mumps are endemic in many countries.
Protection against measles is especially important for persons
planning foreign travel, including adolescents and adults who have
not had measles disease and have not been adequately vaccinated,
and infants aged 6-11 months. Similarly, protection against
rubella is especially important for women of childbearing age who
are not immune to the disease. Although proof of vaccination is
not required for entry into the United States, persons traveling
or living abroad should ensure that they are immune to measles,
rubella, and mumps.

Persons who travel or live abroad and who do not have
acceptable evidence of measles, rubella, and mumps immunity (Table 1)
should be vaccinated with MMR. Children who travel or live
abroad should be vaccinated at an earlier age than recommended for
children remaining in the United States. Before their departure
from the United States, children aged greater than or equal to 12
months should have received two doses of MMR vaccine separated by
at least 28 days, with the first dose administered on or after the
first birthday. Children aged 6-11 months should receive a dose of
monovalent measles vaccine before departure. If monovalent measles
vaccine is not available, no specific contraindication exists to
administering MMR to children aged 6-11 months. However, because
the risk for serious disease from either mumps or rubella
infection among infants is relatively low and because children
aged less than 12 months are less likely to develop serologic
evidence of immunity when vaccinated with measles, mumps, and
rubella antigens than are older children, mumps vaccine and
rubella vaccine generally are administered only to children aged
greater than or equal to 12 months. Children administered
monovalent measles vaccine or MMR before the first birthday should
be considered potentially susceptible to all three diseases and
should be revaccinated with two doses of MMR, the first of which
should be administered when the child is aged 12-15 months (12
months if the child remains in an area where disease risk is high)
and the second at least 28 days later.

Parents who travel or reside abroad with infants aged less
than 12 months should have acceptable evidence of immunity to
rubella and mumps (Table 1), as well as measles, so they will not
become infected if their infants contract these diseases. Infants
aged less than 6 months are usually protected against measles,
rubella, and mumps by maternally derived antibodies and ordinarily
do not require additional protection unless the infant's mother is
diagnosed with measles (see Use of Vaccine and Immune Globulin
Among Persons Exposed to Measles, Rubella, or Mumps).
SPECIAL CONSIDERATIONS FOR VACCINATION

Persons Infected with Human Immunodeficiency Virus (HIV)

Although the risk for measles exposure is currently low in
most areas of the United States and the Western Hemisphere, this
risk remains high in many other regions and measles continues to
be imported into the United States. HIV-infected persons are at
increased risk for severe complications if infected with measles
(126,127). Among HIV-infected persons who did not have evidence of
severe immunosuppression (Table 2), no serious or unusual adverse
events have been reported after measles vaccination (123-126).
Therefore, MMR vaccination is recommended for all asymptomatic
HIV-infected persons who do not have evidence of severe
immunosuppression and for whom measles vaccination would otherwise
be indicated. MMR vaccination should also be considered for all
symptomatic HIV-infected persons who do not have evidence of
severe immunosuppression (Table 2) (128,129). Testing asymptomatic
persons for HIV infection is not necessary before administering
MMR or other measles-containing vaccine (130).

Transient increases in HIV viral load have been observed
after administration of other vaccines to HIV-infected persons
(131,132). The clinical significance of these increases is not
known. Theoretically, a similar increase also may occur after MMR
vaccination of HIV-infected persons.

Because the immunologic response to live and killed-antigen
vaccines may decrease as HIV disease progresses, vaccination early
in the course of HIV infection may be more likely to induce an
immune response (133). Therefore, HIV-infected infants without
severe immunosuppression should routinely receive MMR vaccine as
soon as possible upon reaching the first birthday (i.e., at age 12
months)(130). Consideration should be given to administering the
second dose of MMR vaccine as soon as 28 days (i.e., 1 month)
after the first dose rather than waiting until the child is ready
to enter kindergarten or first grade. In addition, if at risk for
exposure to measles, HIV-infected infants who are not severely
immunocompromised should be administered single-antigen measles
vaccine or MMR vaccine at age 6-11 months. These children should
receive another dose, administered as MMR vaccine, as soon as
possible upon reaching the first birthday, provided at least 1
month has elapsed since the administration of the previous dose of
measles-containing vaccine. An additional dose of MMR vaccine can
be administered as early as 1 month after the second dose. If
otherwise indicated, newly diagnosed HIV-infected children and
adults without acceptable evidence of measles immunity (Table 1)
should receive MMR vaccine as soon as possible after diagnosis,
unless they have evidence of severe immunosuppression (Table 2).
Data indicate that, of the HIV-infected infants born in the United
States annually, approximately 5% (i.e., 50 children per year)
would be classified as severely immunocompromised at age 12
months, when the first dose of MMR vaccine is recommended.

Measles vaccine is not recommended for HIV-infected persons
with evidence of severe immunosuppression (Table 2) for several
reasons:

a case of progressive measles pneumonitis occurred in a person
with AIDS and severe immunosuppression to whom MMR vaccine was
administered (134);

morbidity related to measles vaccination has been reported
among persons with severe immunosuppression unrelated to HIV
infection (135-138); and

in the United States, the incidence of measles is presently
very low.

Serious illness associated with administration of rubella or
mumps vaccines to HIV-infected persons has not been reported. MMR
vaccine is not contraindicated for the close contacts of
immunocompromised persons. All family and other close contacts of
HIV-infected persons should be vaccinated with MMR vaccine, unless
they have acceptable evidence of measles immunity.

Severely immunocompromised patients and other symptomatic
HIV-infected patients who are exposed to measles should receive
immune globulin (IG) prophylaxis regardless of vaccination status
because they may not be protected by the vaccine. For patients
receiving intravenous immune globulin (IGIV) therapy, a standard
dose of 100-400 mg/kg should be sufficient to prevent measles
infection after exposures occurring within 3 weeks after
administration of IGIV; for patients exposed to measles greater
than 3 weeks after receiving a standard IGIV dose, an additional
dose should be considered. Although no data are available
concerning the effectiveness of IGIV in preventing measles, high
dose IGIV may be as effective as immune globulin administered
intramuscularly. Persons receiving regular (e.g., monthly) IGIV
therapy for HIV infection or other indications may not respond to
MMR or its component vaccines because of the continued presence of
high levels of passively acquired antibody (see Precautions and
Contraindications, Recent Administration of Immune Globulin). If
indicated, MMR vaccine should be administered at least 2 weeks
before beginning IGIV therapy.

Use of Vaccine and Immune Globulin Among Persons Exposed to
Measles, Rubella, or Mumps
Use of Vaccine

Exposure to measles is not a contraindication to vaccination.
MMR or measles vaccine, if administered within 72 hours of initial
measles exposure, may provide some protection (139-143). For most
persons aged greater than or equal to 12 months who are exposed to
measles in most settings (e.g., day care facilities, schools,
colleges, health-care facilities), administration of MMR or
measles vaccine is preferable to using immune globulin (IG). For
susceptible persons aged greater than or equal to 6 months who are
0household contacts of measles patients, use of vaccine within 72
hours of initial exposure is also acceptable. However, measles
often is not recognized as such until greater than 72 hours after
onset. Therefore, administration of IG to susceptible household
contacts who are not vaccinated within 72 hours of initial
exposure is recommended (see Use of Immune Globulin). Infants
vaccinated before age 12 months must be revaccinated on or after
the first birthday with two doses of MMR vaccine separated by at
least 28 days (see Routine Vaccination). Measles-containing
vaccine is not recommended for postexposure measles prophylaxis in
immunocompromised persons or pregnant women (see
Contraindications).

Postexposure MMR vaccination does not prevent or alter the
clinical severity of rubella or mumps. However, widespread
vaccination during a mumps outbreak may help terminate such
outbreaks (144).

If exposure to measles, rubella, or mumps does not cause
infection, postexposure vaccination with MMR should induce
protection against subsequent infection. If the exposure results
in infection, no evidence indicates that administration of MMR
vaccine during the presymptomatic or prodromal stage of illness
increases the risk for vaccine-associated adverse events.
Use of Immune Globulin

If administered within 6 days of exposure, IG can prevent or
modify measles in a nonimmune person. However, any immunity
conferred is temporary unless modified or typical measles occurs
(139). The usual recommended dose of IG is 0.25 mL/kg (0.11 mL/lb)
of body weight (maximum dose = 15 mL). However, the recommended
dose of IG for immunocompromised persons is 0.5 mL/kg of body
weight (maximum dose = 15 mL). For persons receiving IGIV therapy,
administration of at least 100 mg/kg within 3 weeks before measles
exposure should be sufficient to prevent measles infection.

IG is indicated for susceptible household contacts of measles
patients, particularly those for whom the risk for complications
is increased (i.e., infants aged less than or equal to 12 months,
pregnant women, or immunocompromised persons). Infants less than
6 months of age are usually immune because of passively acquired
maternal antibodies. However, if measles is diagnosed in a mother,
unvaccinated children of all ages in the household who lack other
evidence of measles immunity should receive IG. IG prophylaxis is
not indicated for household contacts who have received a dose of
measles vaccine on or after the first birthday, unless they are
immunocompromised. Only if administered within 72 hours of initial
measles exposure is MMR vaccine acceptable for postexposure
prophylaxis in household contacts aged greater than or equal to 6
months except pregnant women, immunocompromised patients, and
others for whom vaccine is contraindicated (see Use of Vaccine).
IG should not be used to control measles outbreaks.

Any person exposed to measles who lacks evidence of measles
immunity (Table 1) and to whom IG is administered should
subsequently receive MMR vaccine, which should be administered no
earlier than 5-6 months after IG administration, provided the
person is then aged greater than or equal to 12 months and the
vaccine is not otherwise contraindicated. Passively acquired
measles antibodies can interfere with the immune response to
measles vaccination (see Recent Administration of Immune
Globulins). The interval required to avoid such interference
varies (Table 3).

IG does not prevent rubella or mumps infection after exposure
and is not recommended for that purpose. Although administration
of IG after exposure to rubella will not prevent infection or
viremia, it may modify or suppress symptoms and create an
unwarranted sense of security. Therefore, IG is not recommended
for routine postexposure prophylaxis of rubella in early pregnancy
or any other circumstance. Infants with congenital rubella have
been born to women who received IG shortly after exposure.
Administration of IG should be considered only if a pregnant woman
who has been exposed to rubella will not consider termination of
pregnancy under any circumstances. In such cases, intramuscular
administration of 20 mL of immune globulin within 72 hours of
rubella exposure may reduce -- but will not eliminate -- the risk for
rubella (145,146).

Revaccination of Persons Vaccinated According to Earlier
Recommendations

Some persons vaccinated according to earlier recommendations
for use of measles, rubella, mumps, and MMR vaccines should be
revaccinated to ensure that they are adequately protected. Unless
one of its component vaccines is contraindicated, MMR vaccine
should be used for this purpose.

Previous vaccination with live measles, rubella, and mumps
vaccines. Persons vaccinated with live measles, rubella, or mumps
vaccines before the first birthday who were not revaccinated on or
after the first birthday should be considered unvaccinated. Unless
they have other acceptable evidence of immunity to measles,
rubella, and mumps (Table 1), these persons should be revaccinated
with MMR.

Live attenuated Edmonston B measles vaccine (distributed from
1963 to 1975) was usually administered with IG or high-titer
measles immune globulin (MIG; no longer available in the United
States). Vaccination with this product, administered on or after
the first birthday, is considered an effective first dose of
vaccine. If indicated, a second dose of MMR vaccine should be
administered (see Documentation of Immunity).

IG or MIG administered simultaneously with further attenuated
measles vaccines (i.e., vaccines containing the Schwarz or Moraten
virus strains) may have impaired the immune response to
vaccination. Persons who received measles vaccine of unknown type
or further attenuated measles vaccine accompanied by IG or MIG
should be considered unvaccinated and should be administered two
doses of MMR vaccine. Persons vaccinated with other previously
licensed live rubella vaccines that were not administered with IG
or MIG (i.e., HPV-77 or Cendehill vaccines) need not be
revaccinated against rubella.

Previous vaccination with inactivated measles vaccine or
measles vaccine of unknown type. Inactivated (killed) measles
vaccine was available in the United States only from 1963 to 1967
but was available through the early 1970s in some other countries.
It was frequently administered as a series of two or three
injections. Because persons who received inactivated vaccine are
at risk for developing severe atypical measles syndrome when
exposed to the natural virus, they should receive two doses of MMR
or other live measles vaccine, separated by at least 28 days
(147). Persons who received inactivated vaccine followed within 3
months by live virus vaccine should also be revaccinated with two
more doses of MMR or other live measles vaccine. Revaccination is
particularly important when the risk for exposure to natural
measles virus is increased (e.g., during international travel).

Persons vaccinated during 1963-1967 with vaccine of unknown
type may have received inactivated vaccine and also should be
revaccinated. Persons who received a vaccine of unknown type after
1967 need not be revaccinated unless the original vaccination
occurred before the first birthday or was accompanied by IG or
MIG. However, such persons should receive a second dose before
entering college, beginning work in a health-care facility, or
undertaking international travel.

Some recipients of inactivated measles vaccine who were later
revaccinated with live measles vaccine have had adverse reactions
to the live vaccine; the percentage who reported adverse reactions
ranges from 4% to 55% (148). In most cases, these reactions were
mild (e.g., local swelling and erythema, low-grade fever lasting
1-2 days), but rarely more severe reactions (e.g., prolonged high
fevers, extensive local reactions) have been reported. However,
natural measles infection is more likely to cause serious illness
among recipients of inactivated measles vaccine than is live
measles virus vaccine.

Previous vaccination with inactivated mumps vaccine or mumps
vaccine of unknown type. A killed mumps virus vaccine was licensed
for use in the United States from 1950 through 1978. Although this
vaccine induced antibody, the immunity was transient. The number
of doses of killed mumps vaccine administered between licensure of
live attenuated mumps vaccine in 1967 until the killed vaccine was
withdrawn in 1978 is unknown but appears to have been limited.

Revaccination with MMR should be considered for certain
persons vaccinated before 1979 with either killed mumps vaccine or
mumps vaccine of unknown type who are at high risk for mumps
infection (e.g., persons who work in health-care facilities during
a mumps outbreak). No evidence exists that persons who have had
mumps disease or who have previously received mumps vaccine
(killed or live) are at increased risk for local or systemic
reactions upon receiving MMR or live mumps vaccine.
ADVERSE EVENTS AFTER MMR VACCINATION

Adverse events associated with administration of MMR vaccine
range from local pain, induration, and edema to rare systemic
reactions such as anaphylaxis. Side effects tend to occur among
vaccine recipients who are nonimmune and therefore are very rare
after revaccination (see Revaccination). Expert committees at the
Institute of Medicine (IOM) recently reviewed all evidence
concerning the causal relationship between MMR vaccination and
various adverse events (149,150). The IOM determined that evidence
establishes a causal relation between MMR vaccination and
anaphylaxis, thrombocytopenia, febrile seizures, and acute
arthritis. Although vasculitis, otitis media, conjunctivitis,
optic neuritis, ocular palsies, Guillain-Barre syndrome, and
ataxia have been reported after administration of MMR or its
component vaccines and are listed in the manufacturer's package
insert, no causal relationship has been established between these
events and MMR vaccination.

Evidence does not support a causal association of
administration of measles-containing vaccine with risk for Crohn
disease, a hypothesis proposed by some researchers in the United
Kingdom and Sweden (151-156). Other researchers have been unable
to replicate the laboratory findings that were reported to support
this hypothesized association (157,158). Concerns also have been
raised about the methods used in the epidemiologic studies that
suggested an association between Crohn disease and measles
vaccination (159-163). Other data do not support an association
between measles vaccination and risk for Crohn disease or other
inflammatory bowel disease (164,165).

Infection with mumps virus may trigger the onset of diabetes
mellitus in some persons. However, no association has been
established between vaccination with MMR or other mumps virus
vaccine and pancreatic damage or subsequent development of
diabetes mellitus (150).
Fever, Rash, Lymphadenopathy, or Parotitis

Measles, rubella, and mumps vaccines may cause fever after
vaccination; the measles component of MMR vaccine is most often
associated with this adverse event. Approximately 5% of children
develop a temperature of greater than or equal to 103 F (greater
than or equal to 39.4 C) after MMR vaccination. Such febrile
reactions usually occur 7-12 days after vaccination and generally
last 1-2 days (166). Most persons with fever are otherwise
asymptomatic.

Measles- and rubella-containing vaccines (including MMR) can
cause transient rashes, which usually appear 7-10 days after
vaccination, in approximately 5% of vaccinated persons. Transient
lymphadenopathy sometimes occurs following administration of MMR
or other rubella-containing vaccine, and parotitis has been
reported rarely following administration of MMR or other
mumps-containing vaccine.
Allergic Reactions

Hypersensitivity reactions, usually consisting of urticaria
or a wheal and flare at the injection site, occur rarely after
administration of MMR or any of its component vaccines. Immediate
anaphylactic reactions to these vaccines are very rare. More than
70 million doses of MMR vaccine have been distributed in the
United States since the Vaccine Adverse Events Reporting System
(VAERS) was implemented in 1990. The reported rate of possible
anaphylaxis after vaccination with measles-containing vaccine is
less than 1 case per 1 million doses distributed (CDC, unpublished
data). Allergic reactions including rash, pruritus, and purpura
have been temporally associated with mumps vaccination but are
uncommon, usually mild, and of brief duration.
Thrombocytopenia

Surveillance of adverse reactions in the United States and
other countries indicates that MMR vaccine can, in rare instances,
cause clinically apparent thrombocytopenia within 2 months after
vaccination. In prospective studies, the reported frequency of
clinically apparent thrombocytopenia after MMR vaccination ranged
from 1 case per 30,000 vaccinated children in Finland and Great
Britain (167,168) to 1 case per 40,000 in Sweden (169), with a
temporal clustering of cases occurring 2-3 weeks after
vaccination. Based on passive surveillance, the reported frequency
of thrombocytopenia was approximately 1 case per 100,000 vaccine
doses distributed in Canada (170) and France (171), and
approximately 1 case per 1 million doses distributed in the United
States (172). The clinical course of these cases was usually
transient and benign, although hemorrhage occurred rarely (172).
The risk for thrombocytopenia during rubella or measles infection
is much greater than the risk after vaccination (173). Based on
case reports, the risk for MMR-associated thrombocytopenia may be
increased for persons who have previously had immune
thrombocytopenic purpura, particularly for those who had
thrombocytopenic purpura after an earlier dose of MMR vaccine
(150,174,175).
Neurological Events

Adverse neurological events after administration of MMR
vaccine are rare. Reports of nervous system illness following MMR
vaccination do not necessarily denote an etiologic relationship
between the illness and the vaccine. Although several cases of
sensorineural deafness have been reported after administration of
MMR vaccine, evidence from these case reports (e.g., timing of
onset and other features) is inadequate to accept or reject a
causal relation between MMR vaccination and sensorineural
deafness.
Aseptic Meningitis

Aseptic meningitis has been clearly associated with
administration of the Urabe strain mumps vaccine virus but not
with the Jeryl Lynn strain, which is the only mumps vaccine used
in the United States (176-178). Sentinel surveillance laboratories
in the United Kingdom identified thirteen aseptic meningitis cases
(91 cases per 1 million doses distributed) that occurred after
administration of the Urabe strain vaccine during 1988-1992 (168).
Since the United Kingdom switched to Jeryl Lynn strain vaccine in
1992, no mumps vaccine-associated aseptic meningitis cases have
been reported by the surveillance laboratories (178).
Subacute Sclerosing Panencephalitis (SSPE)

Measles vaccination substantially reduces the occurrence of
SSPE as evidenced by the near elimination of SSPE cases after
widespread measles vaccination. SSPE has been reported rarely
among children who had no history of natural measles infection,
but who had received measles vaccine. Evidence indicates that at
least some of these children had unrecognized measles infection
before they were vaccinated and that the SSPE was directly related
to the natural measles infection. The administration of live
measles vaccine does not increase the risk for SSPE, even among
persons who have previously had measles disease or received live
measles vaccine (150,179).
Encephalopathy/Encephalitis

Encephalitis with resultant residual permanent central
nervous system (CNS) impairment (encephalopathy) develops in
approximately 1 per 1,000 persons infected with measles virus.
Whether attenuated live viral measles vaccine can also produce
such a syndrome has been a concern since the earliest days of
measles vaccine use. In 1994, the IOM noted that most data were
from case reports, case series, or uncontrolled observational
studies, and concluded that the evidence was inadequate to accept
or reject a causal relation (150).

The British National Childhood Encephalopathy Study (NCES)
identified a fourfold elevation in risk for encephalopathy or
convulsions among children who received measles vaccine during
1976-1979, compared with the risk for these conditions among
unvaccinated children (180). Among previously normal children, the
attributable risk for acute encephalopathy or convulsions was 1
case per 87,000 vaccinations. Findings of a subsequent 10-year
follow-up study of persons diagnosed with convulsions or acute
encephalopathy in the NCES indicated little difference in risk for
persisting neurological abnormality among those who had received
measles vaccine compared with those who had not (E. Miller,
personal communication).

Although cases of encephalopathy have been reported after
administration of measles-containing vaccine (181), lack of a
unique clinical syndrome or specific laboratory test has hampered
causality assessment. However, four independent passive
surveillance systems in the United States (i.e., CDC measles
surveillance from 1963 to 1971, the Monitoring System for Adverse
Events Following Immunizations {MSAEFI} from 1979 to 1990, the
Vaccine Adverse Event Reporting System {VAERS} from 1991 to 1996,
and the Vaccine Injury Compensation Program {VICP}) have reported
cases of encephalopathy in which a similar timing of reported
events following vaccine administration is apparent. In all four
case series, onset of encephalopathies follows a non-random
distribution with onset approximately 10 days after vaccination,
a timing consistent with onset of encephalopathy after infection
with wild measles virus (182). Although this pattern may be in
part attributable to consistent biases of these passive
surveillance systems, it is also consistent with a causal
relationship between measles vaccine and encephalopathies (183).
During the period these four systems have collected data, 166
cases of encephalopathy occurring 6-15 days after vaccination have
been identified and an estimated 313 million doses of
measles-containing vaccines have been distributed (i.e.,
approximately 1 case per 2 million doses distributed). Thus,
encephalopathy occurs much less frequently after administration of
measles vaccine than after measles infection.

Febrile Seizures and Personal and Family History of Convulsions

MMR vaccination, like other causes of fever, may cause
febrile seizures. The risk for such seizures is approximately 1
case per 3,000 doses of MMR vaccine administered (168). Studies
have not established an association between MMR vaccination and
residual seizure disorders (150). Although children with personal
or family histories of seizures are at increased risk for
idiopathic epilepsy, febrile seizures after vaccinations do not
increase the probability that epilepsy or other neurologic
disorders will subsequently develop in these children. Most
convulsions that occur after measles vaccination are simple
febrile seizures, which affect children who do not have other
known risk factors for seizure disorders.

Antipyretics may prevent febrile seizures after MMR
vaccination if administered before the onset of fever and
continued for 5-7 days. However, antipyretics are difficult to use
for this purpose because the onset of fever is often sudden and
occurs unpredictably. Seizures can occur early in the course of
fever. Parents should be vigilant for fever that occurs after
vaccination and should be counseled regarding its appropriate
treatment. Use of aspirin during some illnesses in childhood is
associated with the occurrence of Reye syndrome. Therefore,
aspirin generally should not be used to prevent or control fever
among children and adolescents.

The 5%-7% of children who have either a personal history of
convulsions or a parent or sibling with history of convulsions may
be at increased risk for febrile convulsions after MMR vaccination
(184). The precise risk has not been measured, but appears to be
minimal. On the other hand, febrile seizures occur commonly among
children in whom measles disease develops, and the risk for
acquiring measles is substantial. Therefore, the benefits of
administering MMR vaccine to children with a personal or family
history of convulsions substantially outweigh the risks and these
children should be vaccinated following the recommendations for
children who have no contraindications.

Children who are being treated with anticonvulsants should
continue to take them after measles vaccination. Because
protective levels of most currently available anticonvulsant drugs
(e.g., phenobarbital) are not achieved for some time after therapy
is initiated, prophylactic use of these drugs is not feasible.

The parents of children who have either a personal or family
history of seizures should be advised of the benefits of
vaccination and the minimal increased risk for seizures, which
generally occur 5-14 days after measles vaccination.
Guillain-Barre Syndrome (GBS)

Cases of GBS occurring after administration of MMR or its
component vaccines have been reported, but the IOM judged the
evidence insufficient to accept or reject a causal relationship
(150). Recent studies provide evidence against this potential
association (185,186). After recent mass vaccination campaigns
that involved approximately eight million doses of measles-rubella
vaccine in the United Kingdom and greater than 70 million doses of
measles vaccine in Latin America, evaluations of GBS incidence
demonstrated no increases over background rates.

Arthralgia, Arthritis, and Persistent or Recurrent Arthropathy

Joint symptoms are associated with the rubella component of
MMR. Among susceptible persons who receive rubella vaccine,
arthralgia and transient arthritis occur more frequently among
adults than among children and more frequently among postpubertal
females than among males. Acute arthralgia or arthritis are rare
among children who receive RA 27/3 vaccine (187). By contrast,
arthralgia develops among approximately 25% of susceptible
postpubertal females after RA 27/3 vaccination and approximately
10% have acute arthritis-like signs and symptoms (188,189).
Although rare reports of transient peripheral neuritic complaints
have occurred, insufficient evidence exists to indicate a causal
relation between RA 27/3 vaccine and peripheral neuropathies
(149,190). When acute joint symptoms occur, or when pain and/or
paresthesias not associated with joints occur, they generally
begin 1-3 weeks after vaccination, persist for 1 day to 3 weeks,
and rarely recur. Adults who experienced acute joint symptoms
after rubella vaccination usually have not had to disrupt work
activities (189,190,191).

A 1991 report by the IOM stated that although some data were
consistent with a causal relation between RA27/3 rubella vaccine
and chronic arthritis among adult women, the evidence was limited
in scope and confined to reports from a single institution (149).
Several more recently published studies have found no evidence of
increased risk for new onset of chronic arthropathies among women
vaccinated with RA 27/3 vaccine (192-194). In addition, data from
a recent prospective, randomized, placebo-controlled trial by the
same group that initially reported chronic arthropathy after
rubella vaccination demonstrated only a small excess risk for
persistent joint symptoms among persons who received rubella
vaccine (relative risk {RR} = 1.58; 95% confidence interval =
1.01-2.45) (195). Neither the duration of arthropathy nor timing
of onset was reported. The occurrence of arthropathy described as
moderate or severe did not differ between vaccine and placebo
recipients and was rare in both groups.
Interference with Tuberculin Skin Tests

Tuberculin testing is not a prerequisite for vaccination with
MMR or any of its component vaccines. MMR vaccine may interfere
with the response to a tuberculin test (196-198). Therefore,
tuberculin testing, if otherwise indicated, can be done either on
the same day MMR vaccine is administered or 4-6 weeks later.
Revaccination

No evidence indicates that administration of live measles,
mumps, or rubella vaccine increases the risk for adverse reactions
among persons who are already immune to these diseases as a result
of previous vaccination or natural disease. Data indicate that
only persons who are not immune when vaccinated tend to have
postvaccination side effects similar to the disease symptoms
(139). No evidence exists that persons who have previously
received killed mumps vaccine or had mumps disease are at
increased risk for local or systemic reactions from receiving live
mumps vaccine. Some recipients of inactivated measles vaccine who
were later revaccinated with live measles vaccines have had
adverse reactions to the live vaccine (see Revaccination of
Persons Vaccinated According to Earlier Recommendations).
REPORTING ADVERSE EVENTS

Reporting of serious adverse events that occur after
administration of MMR or its component vaccines helps identify
adverse events that may be caused by these vaccines. The National
Childhood Vaccine Injury Act of 1986 requires health-care
providers to report serious adverse events that occur after
vaccination with MMR and its component vaccines to the Vaccine
Adverse Events Reporting System (VAERS). Persons other than
health-care workers can also report adverse events to VAERS.
Events that must be reported after MMR vaccination are listed in
the reportable events table within the Act and include anaphylaxis
or anaphylactic shock occurring within 7 days of vaccination,
encephalopathy (or encephalitis) occurring within 7 days of
vaccination, and any events described in the manufacturer's
package insert as contraindications to additional doses of vaccine
(199). Other adverse events occurring after administration of a
vaccine, especially events that are serious or unusual, also
should be reported to VAERS, regardless of the provider's opinion
of the causality of the association. VAERS reporting forms and
information are available 24 hours a day by calling 1-800-822-7967
or via the World Wide Web at http:\\www.cdc.gov/nip/vaers.htm.
VACCINE INJURY COMPENSATION

The National Vaccine Injury Compensation Program, established
by the National Childhood Vaccine Injury Act of 1986, is a system
under which compensation may be paid on behalf of a person thought
to have been injured or to have died as a result of receiving a
vaccine covered by the program. The program is intended as an
alternative to civil litigation under the traditional tort system
because negligence need not be proven.

The Act establishes a) a Vaccine Injury Compensation Table
that lists the vaccines covered by the program; b) the injuries,
disabilities, and conditions (including death) for which
compensation may be paid without proof of causation; and c) the
period after vaccination during which the first symptom or
substantial aggravation of the injury must appear. Modifications
to the Vaccine Injury Table became effective March 24, 1997 (199).
Persons may be compensated for an injury listed in the established
table or one that can be demonstrated to result from
administration of a listed vaccine. Additional information about
the program is available. *
PRECAUTIONS AND CONTRAINDICATIONS
Pregnancy

MMR and its component vaccines should not be administered to
women known to be pregnant. Because a risk to the fetus from
administration of these live virus vaccines cannot be excluded for
theoretical reasons, women should be counseled to avoid becoming
pregnant for 30 days after vaccination with measles or mumps
vaccines and for 3 months after administration of MMR or other
rubella-containing vaccines. Routine precautions for vaccinating
postpubertal women with MMR should be followed in all vaccination
programs (see Routine Vaccination -- Women of Childbearing Age). If
a pregnant woman is vaccinated or if she becomes pregnant within
3 months after vaccination, she should be counseled about the
theoretical basis of concern for the fetus, but MMR vaccination
during pregnancy should not ordinarily be a reason to consider
termination of pregnancy. Rubella-susceptible women who are not
vaccinated because they state they are or may be pregnant should
be counseled about the potential risk for CRS and the importance
of being vaccinated as soon as they are no longer pregnant.

Because birth defects are noted in 3%-5% of all births,
confusion about the etiology of birth defects may result if
vaccine is administered during pregnancy. Although of theoretical
concern, no cases of congenital rubella syndrome or abnormalities
attributable to infection with measles, rubella, or mumps vaccine
virus infection have been observed among infants born to
susceptible mothers who received any of these vaccines during
pregnancy. From January 1971 through April 1989, CDC followed to
term 321 known rubella-susceptible pregnant women who had been
vaccinated with live rubella vaccine within 3 months before or 3
months after conception. Ninety-four women received HPV-77 or
Cendehill vaccines, one received vaccine of unknown strain, and
226 received RA 27/3 vaccine (the only rubella vaccine presently
used in the United States). None of the 324 infants born to these
mothers had malformations compatible with congenital rubella
infection. This total included five infants who had serologic
evidence of subclinical infection; three of the infants were
exposed to HPV-77 or Cendehill vaccine and two were exposed to RA
27/3 vaccine. Based on these data, the estimated risk for serious
malformations attributable to RA 27/3 rubella vaccine ranges from
zero to 1.6%. If the infants exposed to other rubella vaccines are
included, the estimated risk is zero to 1.2%, substantially less
than the greater than or equal to 20% risk for CRS associated with
maternal infection during the first trimester of pregnancy (200).
Moreover, the observed risk for CRS with both the HPV-77 or
Cendehill and RA 27/3 strains of vaccine is zero.

Rubella vaccine virus has been isolated from the aborted
fetus of one (3%) of 35 rubella-susceptible women who received RA
27/3 strain vaccine during pregnancy. In contrast, vaccine virus
was isolated from the fetuses of 17 (20%) of 85 women to whom
HPV-77 or Cendehill vaccines were administered (201). This finding
provides additional evidence that the RA 27/3 vaccine poses no
greater risk for teratogenicity than did the HPV-77 or Cendehill
vaccines.

Breast feeding is not a contraindication to vaccination.
Although a woman can excrete rubella vaccine virus in breast milk
and transmit the virus to her infant, the infection remains
asymptomatic (202-205). Otherwise, persons who receive MMR or its
component vaccines do not transmit measles, rubella, or mumps
vaccine viruses (206,207). Thus, MMR vaccine can be administered
safely to susceptible children or other persons with household
contacts who are pregnant to help protect these pregnant women
from exposure to wild rubella virus.

All suspected cases of CRS, whether presumed to be due to
wild-virus or vaccine-virus infection, should be reported to state
and local health departments. Suspected or confirmed cases of CRS
can also be reported to the VAERS (see Reporting Adverse Events).
Severe Illness

Because of the importance of protecting susceptible children
against measles, mumps, and rubella, medical personnel should use
every opportunity to vaccinate susceptible persons. The decision
to vaccinate or postpone vaccination of a person who currently has
or recently has had an acute febrile illness depends largely on
the cause of the illness and the severity of symptoms. Minor
illnesses, with or without fever (e.g., diarrhea, upper
respiratory infection, otitis media) are not contraindications for
vaccination and vaccination should not be postponed because of
them. Data indicate that seroconversion rates for each component
of MMR vaccine among persons with mild febrile illness are similar
to those among healthy persons (208,209). Similarly, performing
routine physical examinations or measuring temperatures are not
prerequisites for vaccinating persons who appear to be in good
health. In childhood vaccination programs, appropriate procedures
include a) asking the parent or guardian if the child is ill, b)
postponing vaccination of children who have moderate or severe
febrile illnesses, and c) vaccinating children who do not have
other contraindications.

Vaccination of persons with moderate or severe febrile
illnesses should generally be deferred until they have recovered
from the acute phase of their illness. This wait avoids
superimposing adverse effects of vaccination on the underlying
illness or mistakenly attributing a manifestation of the
underlying illness to the vaccine. Data are generally not
available regarding the safety and immunogenicity of MMR vaccine
among persons with moderate or severe febrile illness.

Persons under treatment for tuberculosis have not experienced
exacerbations of the disease when vaccinated with MMR. Although no
studies have been reported concerning the effect of MMR vaccine on
persons with untreated tuberculosis, a theoretical basis exists
for concern that measles vaccine might exacerbate tuberculosis.
Consequently, before administering MMR to persons with untreated
active tuberculosis, initiating antituberculous therapy is
advisable. Tuberculin testing is not a pre-requisite for routine
vaccination with MMR or other measles-containing vaccines.
Allergies

Among persons who are allergic to eggs, the risk for serious
allergic reactions such as anaphylaxis following administration of
measles- or mumps-containing vaccines is extremely low and
skin-testing with vaccine is not predictive of allergic reaction
to vaccination (210-212). Therefore, skin testing is not required
before administering MMR (or other measles- and mumps-containing
vaccines) to persons who are allergic to eggs. Similarly, the
administration of gradually increasing doses of vaccine is not
required. In the past, persons with a history of anaphylactic
reactions (i.e., hives, swelling of the mouth or throat,
difficulty breathing, hypotension, and shock) following egg
ingestion were considered to be at increased risk for serious
reactions after administration of measles- or mumps-containing
vaccines, which are produced in chick embryo fibroblasts. Although
protocols have been developed for skin testing and vaccination of
persons who experience anaphylactic reactions to egg ingestion,
data indicate that most anaphylactic reactions to measles- and
mumps-containing vaccines are not associated with hypersensitivity
to egg antigens but to other components of the vaccines (213-217).

The literature contains several case reports of persons with
an anaphylactic sensitivity to gelatin who had anaphylactic
reactions after receiving MMR vaccine (218-220). MMR and its
component vaccines contain hydrolyzed gelatin as a stabilizer.
Therefore, extreme caution should be exercised when administering
MMR or its component vaccines to persons who have a history of an
anaphylactic reaction to gelatin or gelatin-containing products.
Before administering MMR or its component vaccines to such
persons, skin testing for sensitivity to gelatin can be
considered. However, no specific protocols for this purpose have
been published.

Because MMR and its component vaccines contain trace amounts
of neomycin (25 ug), persons who have experienced anaphylactic
reactions to topically or systemically administered neomycin
should not receive these vaccines. However, neomycin allergy is
most often manifested as a delayed or cell-mediated immune
response (i.e., a contact dermatitis), rather than anaphylaxis. In
persons who have such a sensitivity, the adverse reaction to the
neomycin in the vaccine is an erythematous, pruritic nodule or
papule appearing 48-96 hours after vaccination. A history of
contact dermatitis to neomycin is not a contraindication to
receiving MMR vaccine. MMR vaccine does not contain penicillin and
therefore a history of penicillin allergy is not a
contraindication to MMR vaccination.

Although anaphylaxis after vaccination is extremely rare and
no anaphylaxis deaths associated with administration of MMR
vaccine have been reported, this adverse event can be life
threatening (150). Epinephrine should be available for immediate
use at any site where vaccines are administered in case symptoms
of anaphylaxis occur.
Thrombocytopenia

Children who have a history of thrombocytopenia or
thrombocytopenic purpura may be at increased risk for developing
clinically significant thrombocytopenia after MMR vaccination
(172,175). Although thrombocytopenia can be life threatening, no
deaths have been reported as a direct consequence of
vaccine-induced thrombocytopenia. The decision to vaccinate with
MMR should depend on the benefits of immunity to measles, mumps,
and rubella and the risks for recurrence or exacerbation of
thrombocytopenia after vaccination or during natural infection
with measles or rubella. The benefits of primary immunization are
usually greater than the potential risks, and administration of
MMR vaccine is justified, particularly with regard to the even
greater risk for thrombocytopenia after measles or rubella
disease. However, avoiding a subsequent dose of MMR vaccine may be
prudent if an episode of thrombocytopenia occurred within
approximately 6 weeks after a previous dose of the vaccine.
Serologic evidence of measles immunity among such persons may be
sought in lieu of MMR vaccination.
Recent Administration of Immune Globulins
Recent evidence indicates that high doses of immune globulins
can inhibit the immune response to measles and rubella vaccine for
3 or more months (221, 222). The duration of this interference
with the immune response depends on the dose of immune globulin
administered. The effect of immune globulin preparations on the
response to mumps vaccine is unknown. Blood (e.g., whole blood,
packed red blood cells, and plasma) and other antibody-containing
blood products (e.g., IG, specific immune globulins, and IGIV) can
reduce the immune response to MMR or its component vaccines.
Therefore, these vaccines should be administered to persons who
have received an immune globulin preparation only after the
recommended intervals have elapsed (Table 3) (80). However,
postpartum administration of MMR or rubella vaccine to women who
are susceptible to rubella should not be delayed because
anti-Rho(D) immune globulin (human) or any other blood product was
received during the last trimester of pregnancy or at delivery.
Such rubella-susceptible women should be vaccinated immediately
after delivery and tested at least 3 months later to ensure that
they are immune to rubella and measles.

Immune globulin preparations generally should not be
administered simultaneously with MMR or its component vaccines. If
administration of an immune globulin preparation becomes necessary
because of imminent exposure to disease, MMR or its component
vaccines can be administered simultaneously with the IG
preparation, although vaccine-induced immunity may be compromised.
Usually, vaccine virus replication and stimulation of immunity
will occur 1-2 weeks after vaccination. Thus, if the interval
between administration of any of these vaccines and administration
of an IG preparation is less than 14 days, vaccination should be
repeated after the recommended interval (Table 3), unless
serologic testing indicates that the vaccinated person's immune
system has produced antibodies to each vaccine component (i.e.,
measles, rubella, and mumps). The vaccine should be administered
at an anatomic site remote from that chosen for the IG injection.
Altered Immunocompetence

Enhanced replication of vaccine viruses may occur in persons
who have immune deficiency diseases and in other persons who are
immunosuppressed. Severe immunosuppression may be caused by many
disease conditions (e.g., congenital immunodeficiency, HIV
infection, hematologic or generalized malignancy) and by therapy
with immunosuppressive agents, including large doses of
corticosteroids. For some of these conditions, all affected
persons are severely immunocompromised. For other conditions
(e.g., HIV infection), the degree to which the immune system is
compromised depends on the severity of the condition, which in
turn depends on the disease or treatment stage. Ultimately, the
patient's physician must assume responsibility for determining
whether the patient is severely immunocompromised based on
clinical and laboratory assessment.

Case reports have linked vaccine-associated measles infection
to the deaths of some severely immunocompromised persons
(150,223). Therefore, MMR vaccine should not be administered to
severely immunocompromised persons. To reduce the risk for
measles, rubella, and mumps exposure of immunocompromised
patients, their susceptible close contacts should be vaccinated
with MMR. No case reports exist linking MMR or mumps- or
rubella-containing vaccines with clinically significant infection
caused by mumps or rubella vaccine virus among immunocompromised
vaccine recipients.
HIV-Infected Persons

Among asymptomatic and symptomatic HIV-infected patients who
are not severely immunosuppressed, MMR vaccination has been
associated with variable antibody responses but not with severe or
unusual adverse events. Asymptomatic persons do not need to be
evaluated and tested for HIV infection before MMR and other
measles-containing vaccines are administered. MMR vaccine is
recommended for all asymptomatic HIV-infected persons who are not
severely immunosuppressed and who lack evidence of measles
immunity. MMR vaccination of symptomatic HIV-infected persons
should be considered if they a) do not have evidence of severe
immunosuppression and b) lack evidence of measles immunity. MMR
and other measles-containing vaccines are not recommended for
HIV-infected persons with evidence of severe immunosuppression
(see Special Considerations for Vaccination -- Persons Infected with
Human Immunodeficiency Virus {HIV}) (Table 2).
Steroids

Systemically absorbed corticosteroids can suppress the immune
system of an otherwise healthy person. However, neither the
minimum dose nor the duration of therapy sufficient to cause
immune suppression are well defined. Most experts agree that
steroid therapy usually does not contraindicate administration of
live virus vaccines such as MMR and its component vaccines when
therapy is: a) short term (i.e., less than 14 days)
low-to-moderate dose; b) low-to-moderate dose administered daily
or on alternate days; c) long term alternate day treatment with
short-acting preparations; d) physiologic maintenance doses
(replacement therapy); or e) administered topically (skin or
eyes), by aerosol, or by intra-articular, bursal, or tendon
injection. Although the immunosuppressive effects of steroid
treatment vary, many clinicians consider a steroid dose that is
equivalent to or greater than a prednisone dose of 2 mg/kg of body
weight per day or a total of 20 mg per day sufficiently
immunosuppressive to raise concern about the safety of
administration of live virus vaccines. Persons who have received
systemic corticosteroids in these or greater doses daily or on
alternate days for an interval of greater than or equal to 14 days
should avoid vaccination with MMR and its component vaccines for
at least 1 month after cessation of steroid therapy. Persons who
have received prolonged or extensive topical, aerosol, or other
local corticosteroid therapy that causes clinical or laboratory
evidence of systemic immunosuppression should also avoid
vaccination with MMR for at least 1 month after cessation of
therapy. Persons who receive doses of systemic corticosteroids
equivalent to a prednisone dose of greater than or equal to 2
mg/kg of body weight or greater than or equal to 20 mg total daily
or on alternate days during an interval of less than 14 days
generally can receive MMR or its component vaccines immediately
after cessation of treatment, although some experts prefer waiting
until 2 weeks after completion of therapy. MMR or its component
vaccines generally should not be administered to persons who have
a disease that, in itself, suppresses the immune response and who
are receiving either systemic or locally administered
corticosteroids.
Leukemia

Persons with leukemia in remission who were not immune to
measles, rubella, or mumps when diagnosed with leukemia may
receive MMR or its component vaccines. At least 3 months should
elapse after termination of chemotherapy before administration of
the first dose of MMR vaccine.

Management of Patients with Contraindications to Measles Vaccine

If immediate protection against measles is required for
persons with contraindications to measles vaccination, 0.25 mL/kg
(0.11 mL/lb) of body weight (maximum dose = 15 mL) of IG should be
administered as soon as possible after known exposure (See Use of
Vaccine and Immune Globulin Among Persons Exposed to Measles,
Rubella, or Mumps). Exposed symptomatic HIV-infected and other
immunocompromised persons should receive IG regardless of their
previous vaccination status. Because IG in usual doses may not be
effective for immunocompromised persons, the recommended dose is
0.5 mL/kg of body weight if IG is administered intramuscularly
(maximum dose = 15 mL). This corresponds to a dose of IgG protein
of approximately 82.5 mg/kg (maximum dose = 2,475 mg).
Intramuscular IG may not be needed if a patient is receiving at
least 100-400 mg/kg IGIV at regular intervals and exposure occurs
within 3 weeks after administration of the last dose of IGIV.
Because the amounts of protein administered are similar, high-dose
IGIV may be as effective as intramuscular IG. However, no data are
available concerning the effectiveness of IGIV in preventing
measles.

The effectiveness of IG or IGIV for preventing mumps or
rubella is unknown. These products should not be used for
prophylaxis among immunocompromised persons exposed to these
diseases.
SURVEILLANCE AND OUTBREAK CONTROL

Surveillance for vaccine preventable diseases has four
primary purposes: a) to provide important data on program progress
and long term trends, b) to provide the basis for changes in
disease prevention strategies, c) to help define groups in
greatest need of vaccination, and d) to evaluate vaccine safety
and effectiveness (e.g., protective efficacy, duration of
vaccine-induced immunity, and occurrence of adverse effects). As
the incidence of measles, rubella, and mumps declines in the
United States, enhanced surveillance becomes increasingly
important.

Any person aware of a suspected or known cases of measles,
rubella, congenital rubella syndrome, or mumps should report the
case to the local or state health department. The designated
public health authorities should investigate the case immediately.
The purpose of the investigation is to classify the case, identify
the characteristics of the case and the source of exposure, and
prevent further spread.

Cases of measles, rubella, and congenital rubella syndrome
are reportable in all states, and mumps is reportable in most
states. Data from measles, rubella, congenital rubella syndrome,
and mumps cases are routinely reported by state and local health
departments to CDC and published weekly in the Morbidity and
Mortality Weekly Report.
Measles Case Investigation and Outbreak Control
Case Definition

A suspected measles case is defined as any febrile illness
accompanied by rash. Suspected and known cases of measles should
be reported immediately to the local or state health department.
The designated public health authorities should quickly initiate
an investigation of the reported case. Rapid case reporting and
investigation can help limit further transmission.

A clinical case of measles is defined as an illness
characterized by

a generalized rash lasting greater than or equal to 3 days, and

a temperature of greater than or equal to 38.3 C (greater than
or equal to 101 F), and

cough, coryza, or conjunctivitis.

A probable case of measles

meets the clinical case definition for measles, and

is not epidemiologically linked to a confirmed case, and

has not been serologically or virologically tested or has
noncontributory serologic or virologic results.

A confirmed case of measles

meets the laboratory criteria for measles or

meets the clinical case definition and is epidemiologically
linked to a confirmed case.

Confirmed measles cases are routinely reported to CDC by
state health departments.

Laboratory Diagnosis

The laboratory criteria for measles diagnosis are:

a positive serologic test for measles IgM antibody, or

a significant rise in measles antibody level by any standard
serologic assay, or

isolation of measles virus from a clinical specimen.

A laboratory-confirmed case need not meet the clinical case
definition. Serologic confirmation should be attempted for every
suspected case of measles and is particularly important for any
case that cannot be epidemiologically linked through a chain of
transmission to a confirmed case. However, reporting of suspected
or probable cases, investigation of cases, and the implementation
of control activities should not be delayed pending laboratory
results.

Blood for serologic testing should be collected during the
first clinical encounter with a person who has suspected or
probable measles. The serum should be tested for measles IgM
antibody as soon as possible using an assay that is both sensitive
and specific (e.g., direct-capture IgM EIA method). Correct
interpretation of serologic data depends on the timing of specimen
collection in relation to rash onset and on the characteristics of
the antibody assay used. This timing is especially important for
interpreting negative results because IgM antibody may not be
detectable with some less sensitive assays until at least 72 hours
after rash onset. Measles IgM may be detectable at the time of
rash onset, peaks approximately 10 days after rash onset, and is
usually undetectable 30-60 days after rash onset. In general, if
measles IgM is not detected in a serum specimen obtained in the
first 72 hours after rash onset from a person whose illness meets
the clinical case definition for measles, another specimen should
be obtained at least 72 hours after rash onset and tested for
measles IgM antibody. Measles IgM is detectable for at least 1
month after rash onset. Persons with febrile rash illnesses who
are seronegative for measles should be tested for rubella.

As measles becomes rare in the United States, the likelihood
of obtaining false positive serologic results from measles IgM
antibody testing increases. False positive results have been
obtained by using a commercially available ELISA assay for measles
IgM in persons with parvovirus infection (fifth disease) (224).
Confirmatory testing by using an assay that is both sensitive and
specific (e.g., direct-capture IgM EIA method) should be
considered when IgM is detected in a patient with suspected
measles who has no identified source of infection and no
epidemiologic linkage to another confirmed case. The Measles Virus
Laboratory of CDC's National Center for Infectious Diseases has
provided training to all state public health laboratories to
perform such testing.

Serologic diagnosis of measles can also be confirmed by a
significant rise in antibody titer between acute- and
convalescent-phase serum specimens. Typically, the acute-phase
serum specimen is obtained within 1-3 days after rash onset and
the convalescent-phase specimen is obtained approximately 2-4
weeks later. This method has been largely supplanted by IgM assays
which can be done on a single serum specimen obtained soon after
rash onset.

Asymptomatic measles reinfection can occur among persons who
have previously developed antibodies from vaccination or from
natural disease. Symptomatic reinfections accompanied by rises in
measles antibody titers are rare, and those resulting in
detectable measles IgM antibody occur even more rarely.

Molecular characterization of measles virus isolates has
become an important tool for defining the epidemiologic features
of measles during periods of low disease incidence and for
documenting the impact of measles elimination efforts (16). In
addition to serologic confirmation, a specimen (e.g., urine or
nasopharyngeal mucus) for measles virus isolation and genetic
characterization should be collected as close to the time of rash
onset as possible. Delay in collection of these clinical specimens
reduces the chance of isolating measles virus. Clinicians who have
a patient with suspected measles should immediately contact their
local or state health departments concerning additional
information about collecting and shipping urine and nasal
specimens for measles virus isolation. Molecular characterization
of the measles virus isolated from urine or nasopharyngeal
specimens requires considerable time and cannot be used for
diagnosis of measles. Use of oral fluid in tests for detecting
measles IgM and IgG antibodies is being investigated (225).
Measles Outbreak Control

The local or state health department should be contacted
immediately when suspected cases of measles occur in a community.
All reports of suspected measles cases should be investigated
promptly. Because of the potential for rapid spread of the
disease, one confirmed case of measles in a community is an urgent
public health situation. Once a case is confirmed, prompt
vaccination of susceptible persons at risk for exposure may help
prevent dissemination of measles. Control activities should not be
delayed pending the return of laboratory results from persons with
suspected or probable cases. Persons who cannot readily provide
acceptable evidence of measles immunity (Table 1) should be
vaccinated or excluded from the setting of the outbreak (e.g.,
school, day care facility, hospital, clinic). Almost all persons
who are excluded from an outbreak area because they lack
acceptable evidence of immunity quickly comply with vaccination
requirements. Persons exempted from measles vaccination for
medical, religious, or other reasons should be excluded from
involved institutions in the outbreak area until 21 days after the
onset of rash in the last case of measles. Mass revaccination of
entire communities generally is not necessary. Staff of the
National Immunization Program, CDC, are available to assist health
departments in developing an outbreak control strategy.
Measles Outbreaks Among Preschool-Aged Children

Although most infants are protected from measles by maternal
antibody, the disease is often more severe when it affects
children aged less than 12 months. If cases are occurring among
infants aged less than 12 months, measles vaccination of infants
aged as young as 6 months may be undertaken as an outbreak control
measure. Monovalent measles vaccine is preferred, but MMR vaccine
may be administered if the monovalent vaccine is not readily
available (see Routine Vaccination -- International Travel).
Children vaccinated with measles or MMR vaccine before the first
birthday should be revaccinated at age 12-15 months and again
before entering school.

Passive immunization with IG may be preferred for infants
aged less than 12 months who are household contacts of measles
patients, both because it is likely they will have been exposed
greater than 72 hours before diagnosis of the disease in the
household member and because they are at highest risk for
complications from the disease (see Use of Vaccine and Immune
Globulin Among Persons Exposed to Measles, Rubella, or Mumps). IG
should not be used to control measles outbreaks.

Measles Outbreaks in Day Care Facilities, Schools, and Other
Educational Institutions

During an outbreak in a day care facility, revaccination with
MMR is recommended for all attendees and their siblings who have
not received two doses of measles-containing vaccine on or after
the first birthday and who do not have other evidence of measles
immunity. Facility personnel (e.g., employees, volunteers, service
providers) who cannot provide acceptable evidence of immunity
(Table 1) also should be vaccinated with MMR. Revaccination also
should be considered for unaffected child care facilities in the
community that may be at risk for measles exposure and
transmission.

During outbreaks in schools (elementary, middle, junior and
senior high schools, colleges and other institutions of higher
education), a program of revaccination with MMR vaccine is
recommended in the involved schools. Revaccination of students and
personnel of unaffected schools in the same geographic area who
may be at risk for measles transmission also should be considered.
Revaccination should include all students and their siblings and
all school personnel born during or after 1957 who cannot provide
documentation of adequate measles vaccination or other acceptable
evidence of measles immunity. For persons born in 1957 or later,
adequate vaccination consists of two doses of measles-containing
vaccine separated by at least 28 days with the first dose
administered no earlier than the first birthday (Table 1) (see
Documentation of Immunity). Persons who cannot readily provide
documentation of acceptable evidence of measles immunity should be
vaccinated or excluded from the day care facility, school, or
other educational institution. Revaccinated persons, as well as
persons who receive their first dose as part of the outbreak
control program, may be readmitted to school immediately. Persons
exempted from measles vaccination for medical, religious, or other
reasons, and those who refuse vaccination for any reason, should
be excluded from the day care facility, school, or other
educational institution until 21 days after the onset of rash in
the last case of measles.
Measles Outbreaks in Health-Care Settings

If a measles outbreak occurs within a health-care facility
(e.g., hospital, clinic, physician office) or in the areas served
by the facility, all persons working at the facility who cannot
provide documentation of two doses of measles-containing vaccine
separated by at least 28 days with the first dose administered on
or after the first birthday, or who do not have other evidence of
measles immunity (Table 1), should receive a dose of MMR vaccine.
If indicated, health-care workers born during or after 1957 should
receive a second dose of MMR vaccine at least 28 days after the
previous dose (see Documentation of Immunity). Some health-care
workers born before 1957 have acquired measles in health-care
facilities and have transmitted the disease to patients or
coworkers (see Health-care Facilities). Therefore, during
outbreaks, health-care facilities also should strongly consider
recommending a dose of MMR vaccine to unvaccinated health-care
workers born before 1957 who do not have serologic evidence of
immunity or a history of measles disease.

Serologic testing of health-care workers before vaccination
is not generally recommended during an outbreak because arresting
measles transmission requires rapid vaccination of susceptible
health-care workers. The need to screen, wait for results, and
then contact and vaccinate susceptible persons can impede the
rapid vaccination needed to curb the outbreak.

Susceptible health-care workers (Table 1) exposed to measles
should receive a dose of MMR vaccine and should be removed from
all patient contact and excluded from the facility from the fifth
to the 21st day after the exposure. They may return to work on the
22nd day after exposure. However, susceptible health-care workers
who are not vaccinated after exposure should be removed from all
patient contact and excluded from the facility from the fifth day
after their first exposure to the 21st day after the last
exposure, even if they receive postexposure IG. Personnel who
become ill with prodromal symptoms or rash should be removed from
all patient contact and excluded immediately from the facility
until 4 days after the onset of their rash.
Use of Quarantine

Imposing quarantine measures for outbreak control is usually
both difficult and disruptive to schools and other organizations.
Under special circumstances (i.e., during outbreaks in schools
attended by large numbers of persons who refuse vaccination),
restriction of an event or other quarantine measures might be
warranted (226). However, such action is not recommended as a
routine measure for control of most outbreaks.
Rubella Case Investigation and Outbreak Control
Case Definition

A suspected rubella case is any generalized rash illness of
acute onset. A clinical case of rubella is defined as an illness
characterized by all of the following clinical features:

acute onset of generalized maculopapular rash; and

a temperature of greater than 37.2 C (greater than 99 F), if
measured; and

arthralgia/arthritis, or lymphadenopathy, or conjunctivitis.

Cases meeting the measles case definition are excluded, as
are cases with serologic findings compatible with recent measles
virus infection.
A probable case of rubella

meets the clinical case definition for rubella, and

has no or noncontributory serologic or virologic testing, and

is not epidemiologically linked to a laboratory-confirmed case.

A confirmed rubella case

meets the laboratory criteria for rubella, or

meets the clinical case definition and is epidemiologically
linked to a laboratory confirmed case.

Suspected and known rubella cases should be reported
immediately to local health departments. Aggressive case finding
and intensified surveillance for CRS should follow. Rubella
surveillance is complicated by the nonspecific nature of the
symptoms of the clinical disease. Rubella can be confused with
other illnesses, including measles. Thus, all rubella cases,
particularly isolated cases that do not occur as part of an
outbreak, should be confirmed by laboratory testing. Confirmed
rubella cases are reported to the CDC by state health departments.
Cases of febrile rash illness that are laboratory-negative for
rubella may be measles (rubeola) and the patients should be tested
for measles IgM.

Laboratory confirmation of suspected cases of CRS also is
necessary because the constellation of findings of CRS varies.
Case reports of indigenous congenital rubella syndrome are
sentinel events, indicating the presence of rubella infections in
the community that may previously have been unrecognized. The
diagnosis of one or more indigenous CRS cases in a community
should trigger intensified rubella and CRS surveillance.

A confirmed case of CRS has laboratory confirmation of
rubella infection and at least one defect in each of the two
following categories: a) cataracts/congenital glaucoma (either or
both count as one), congenital heart disease, loss of hearing,
pigmentary retinopathy; and, b) purpura, splenomegaly, jaundice,
microcephaly, mental retardation, meningoencephalitis, radiolucent
bone disease.

A probable case of CRS has any two conditions listed in
category a) or one from category a) and one from category b) and
lacks evidence of any other etiology. A case with laboratory
evidence of rubella infection but no clinical symptoms or signs of
CRS is classified "infection only."
Laboratory Diagnosis

The criteria for laboratory diagnosis of rubella are

a positive serologic test for rubella IgM antibody; or

a significant rise between acute- and convalescent-phase titers
in serum rubella IgG antibody level by any standard serologic
assay; or

the isolation of rubella virus from an appropriately collected
clinical specimen.

The clinical diagnosis of acute rubella should be confirmed
by laboratory testing (230). The demonstration of rubella-specific
IgM antibody is the most commonly used method to obtain serologic
confirmation of acute rubella infection. Rubella-specific IgM
antibody usually becomes detectable shortly after rash onset. The
IgM antibody peaks approximately 7 days after rash onset and
remains detectable for 4-12 weeks, although it is more likely to
be detectable if the serum specimen is obtained within 4-5 weeks
after rash onset. Occasionally, rubella-specific IgM antibody can
be detected up to 1 year after acute infection.

To test for IgM, one serum specimen can be obtained as early
as 1-2 days after rash onset. If IgM is not detectable in this
first specimen, a second serum specimen should be collected 5 days
after the onset of rash or as soon as possible thereafter.
False-negative rubella IgM antibody test results may sometimes
occur even if the specimen is appropriately drawn. False-positive
IgM test results may occur among persons with certain viral
infections (e.g., acute infectious mononucleosis, cytomegalovirus,
or parvovirus) and among persons who are rheumatoid factor
positive.

For IgG assays, the criteria for a significant rise in
rubella antibody level vary by type of assay and by laboratory.
For HI assays, a fourfold rise in the titer of antibody indicates
recent infection. The acute-phase serum specimen should be
obtained as soon after rash onset as possible, preferably within
7 days. The convalescent-phase serum specimen should be drawn at
least 10 days after the acute-phase serum specimen. The acute- and
convalescent-phase serum specimens should be tested simultaneously
in the same laboratory. If the acute-phase serum specimen is drawn
greater than 7 days (and occasionally even if obtained within 7
days) after rash onset, a significant rise in antibody titer may
not be detected by most commonly used IgG assays.

In the absence of rash illness, the diagnosis of subclinical
cases of rubella can be facilitated by obtaining the acute-phase
serum specimen as soon as possible after exposure. The
convalescent-phase specimen should be drawn at least 28 days after
exposure. If acute- and convalescent-phase paired sera provide
inconclusive results, rubella-specific IgM antibody testing can be
performed. Expert consultation may be necessary to interpret the
data.

Among pregnant women of unknown immune status who experience
a rash illness or who are exposed to rubella, laboratory
confirmation of rubella infection may be difficult. A serum
specimen should be obtained as soon as possible. Unfortunately,
serologic results are often nonconfirmatory. Such situations can
be avoided by performing routine prenatal serologic screening of
women who do not have acceptable evidence of rubella immunity (see
Documentation of Immunity and Women of Childbearing Age). In
addition, health-care providers should request that laboratories
performing prenatal serologic screening retain such specimens
until delivery, in case retesting is necessary.
Congenital Rubella

Suspected cases of CRS should be managed with contact
isolation (228). While diagnostic confirmation is pending,
children with suspected CRS should be cared for only by personnel
known to be immune to rubella. Confirmation of diagnosis by virus
isolation can be done by culturing nasopharyngeal and urine
specimens. Serologic confirmation can be obtained by testing cord
blood for the presence of rubella-specific IgM antibodies. An
alternative method for infants aged greater than or equal to 3
months is to document rubella-specific antibody levels that do not
decline at the rate expected from passive transfer of maternal
antibody (i.e., the equivalent of a twofold decline in HI titer
per month). However, some infected infants may have low antibody
levels because of agammaglobulinemia or dysgammaglobulinemia.

In some infants with CRS, rubella virus can persist and can
be isolated from nasopharyngeal and urine cultures throughout the
first year of life or longer (229). Children with CRS should be
presumed infectious at least through the first year of life unless
nasopharyngeal and urine cultures are negative for virus after age
3 months (230). Some authorities suggest that an infant who has
CRS should be considered infectious until two cultures of clinical
specimens obtained 1 month apart are negative for rubella virus
(230). Precautions should be taken to ensure that infants with CRS
do not cause additional rubella outbreaks. Specifically, all
persons who have contact with a child with CRS (e.g., care givers,
household contacts, medical personnel, laboratory workers) should
be immune to rubella (Table 1) (see Documentation of Immunity and
Routine Vaccination).
Rubella Outbreak Control

Outbreak control is important for eliminating CRS. Aggressive
responses to outbreaks may interrupt chains of transmission and
can increase vaccination coverage among persons who might not be
protected otherwise. Although methods for controlling rubella
outbreaks are evolving, the main strategy should be to define
target populations for rubella vaccination, ensure that
susceptible persons within the target populations are vaccinated
rapidly (or excluded from exposure if a contraindication to
vaccination exists), and maintain active surveillance to permit
modification of control measures as needed.

Control measures should be implemented as soon as a case of
rubella is confirmed in a community. This approach is especially
important in any outbreak setting involving pregnant women (e.g.,
obstetric-gynecologic and prenatal clinics). All persons at risk
who cannot readily provide laboratory evidence of immunity or a
documented history of vaccination on or after the first birthday
should be considered susceptible and should be vaccinated unless
vaccination is contraindicated (Table 1) (see Documentation of
Immunity).

Rubella Outbreaks in Schools or Other Educational Institutions

An effective means of terminating rubella outbreaks and
increasing rates of vaccination quickly is to exclude from
possible contact persons who cannot provide valid evidence of
immunity. Experience with measles outbreak control indicates that
almost all students who are excluded from school because they lack
evidence of immunity quickly comply with vaccination requirements
and are promptly readmitted to school. Persons exempted from
rubella vaccination for medical, religious, or other reasons
should also be excluded from attendance. Exclusion should continue
for 3 weeks after the onset of rash of the last reported case in
the outbreak setting. Less rigorous approaches (e.g., voluntary
appeals for vaccination) have not been effective in terminating
outbreaks.
Rubella Outbreaks in Health-Care Settings

During rubella outbreaks in health-care settings where
pregnant women may be exposed, mandatory exclusion and vaccination
of health-care workers who lack evidence of rubella immunity
(Table 1) should be practiced. Exposed health-care workers who
lack evidence of immunity should be excluded from duty from the
seventh day after first exposure through the twenty-first day
after their last exposure or until 5 days after the rash appears.
In addition, because birth before 1957 does not guarantee rubella
immunity, health-care facilities should strongly consider
recommending a dose of MMR vaccine to unvaccinated health-care
workers born before 1957 who do not have serologic evidence of
immunity. Although rubella vaccination during an outbreak has not
been associated with substantial personnel absenteeism (116,191),
vaccination of susceptible persons before an outbreak occurs is
preferable because vaccination causes far less absenteeism and
disruption of routine work activities than does rubella infection.
Mumps Case Investigation and Outbreak Control
Case Definition

A clinical case of mumps is defined as an illness
characterized by acute onset of unilateral or bilateral tender,
self-limited swelling of the parotid or other salivary gland
lasting greater than or equal to 2 days, and without other
apparent cause (as reported by a health professional).

A probable case of mumps

meets the clinical case definition of mumps, and

is not epidemiologically linked to a confirmed or probable
case, and

has noncontributory or no serologic or virologic testing.

A confirmed case of mumps

meets the laboratory criteria for mumps, or

meets the clinical case definition and is epidemiologically
linked to a confirmed or probable case.

A laboratory-confirmed case need not meet the clinical case
definition. Two probable cases that are epidemiologically linked
are considered confirmed, even in the absence of laboratory
confirmation.

Reporting of mumps often has been based solely on clinical
diagnosis without laboratory confirmation. However, parotitis may
have other infectious and noninfectious causes. Therefore,
serologic confirmation of the diagnosis is preferred. Use of
criteria for clinical diagnosis that are both stricter and more
reliable, combined with laboratory confirmation, can be expected
to decrease the number of false positive mumps cases reported and
allow a more accurate assessment of mumps incidence.

Probable or confirmed cases of mumps should be reported
immediately to state and local health departments. Recommended
procedures to enhance the comprehensiveness of reporting include
identification of all contacts, follow-up of susceptible contacts,
and serologic testing of all probable cases to confirm the
diagnosis.
Laboratory Diagnosis

The laboratory criteria for the diagnosis of mumps are

isolation of the mumps virus from a clinical specimen, or

a significant rise between acute and convalescent-phase titers
in serum mumps IgG antibody level by any standard serologic assay,
or

a positive serologic test for mumps IgM antibody.

In a prospective study in the practices of family
practitioners in a Canadian community, one-third of persons with
clinically diagnosed cases of mumps had no serologic evidence of
recent mumps infection (28). Serum mumps IgM IFA tests are
commercially available. However, until more data are available
concerning the use and interpretation of these tests, laboratory
confirmation of mumps should be based on tests of demonstrated
reliability. State health department laboratories can provide
guidance when testing for acute mumps infection is necessary.
Mumps Outbreak Control

The strategy for outbreak control includes three main
elements. The target population (transmission setting) must be
defined. Persons within the population who are susceptible to
mumps must be identified and vaccinated. Consideration should be
given to excluding susceptible persons who are exempt from
vaccination (for medical, religious, or other reasons) from the
affected institution or setting until the outbreak is terminated.
Active surveillance for mumps should be conducted until two
incubation periods (i.e., 5-6 weeks) have elapsed since onset of
the last case.
School-based Mumps Outbreaks

Exclusion of susceptible students from schools affected by a
mumps outbreak (and other, unaffected schools judged by local
public health authorities to be at risk for transmission of the
disease) should be considered among the means to control mumps
outbreaks. Excluded students can be readmitted immediately after
they are vaccinated. Experience with outbreak control for other
vaccine-preventable diseases indicates that almost all students
who are excluded from the outbreak area because they lack evidence
of immunity quickly comply with requirements and can be readmitted
to school. Pupils who have been exempted from mumps vaccination
for medical, religious, or other reasons should be excluded until
at least 26 days after the onset of parotitis in the last person
with mumps in the affected school.
Mumps Outbreaks in Health-Care Settings

Sporadic nosocomial cases of mumps have occurred in long-term
care facilities housing adolescents and young adults (122).
However, mumps virus is less transmissible than measles and other
respiratory viruses. The low level of mumps transmission in the
community results in a low risk for introduction of the disease
into health-care facilities. Because mumps is shed by infected
persons before clinical symptoms become evident and because
infected persons often remain asymptomatic, an effective routine
MMR vaccination program for health-care workers is the best
approach to prevent nosocomial transmission.

To prevent droplet transmission of the disease, respiratory
isolation precautions for persons with mumps should be maintained
for 9 days after onset of symptoms (e.g., parotitis). If exposed
to mumps, health-care workers who lack acceptable evidence of
immunity (Table 1) should be excluded from the health-care
facility from the 12th day after the first exposure through the
26th day after the last exposure. Workers in whom the disease
develops should be excluded from work until 9 days after the onset
of symptoms.

Johnson CE, Kumar ML, Whitwell J, et al. Antibody persistence
after primary measles-mumps-rubella vaccine and response to a
second dose given at four to six vs. eleven to thirteen years.
Pediatr Infect Dis J 1996;15:687-92.

Bottinger M. Immunity to rubella before and after vaccination
against measles, mumps and rubella(MMR) at 12 years of age of the
first generation offered MMR vaccination in Sweden at 18 months.
Vaccine 1995;13:1759-62.

Hatziandreu EJ, Brown RE, Halpern MT. A cost benefit analysis
of the measles-mumps-rubella (MMR) vaccine. Final report prepared
for National Immunization Program, Centers for Disease Control and
Prevention. Arlington, VA: Center for Public Health Research and
Evaluation, Battelle Memorial Institute, 1994.

King GE, Hadler SC. Simultaneous administration of childhood
vaccines: an important public health policy that is safe and
efficacious. Pediatr Infect Dis J 1994;13:394-407.

Shinefield HR, Black S, Morozumi P, et al. Safety and
immunogenicity of concomitant separate administration of MMR-II,
DTP with Hib conjugate and varicella vaccines vs. concomitant
injections of MMR-II and DTP with Hib conjugate vaccines with
varicella vaccine given six weeks later (Abstract). In Program and
abstracts, Third International Conference on the Varicella-Zoster
Virus. Palm Beach Gardens, FL: March 9-11, 1997.

CDC. 1994 Revised classification system for human
immunodeficiency virus infection in children less than 13 years of
age; Official authorized addenda: human immunodeficiency virus
infection codes and official guidelines for coding and reporting
ICD-9-CM. MMWR 1994;43(RR-12):1-19.

CDC. Use of vaccines and immune globulins in persons with
altered immunocompetence: recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR 1993;42(No.
RR-5)1-5.

Alderslade R, Bellman MH, Rawson NSB, et al. The National
Childhood Encephalopathy Study: a report on 1000 cases of serious
neurological disorders in infants and young children from the NCES
research team. In: Department of Health and Social Security.
Whooping cough: reports from the Committee on the Safety of
Medicines and the Joint Committee on Vaccination and Immunization.
London: Her Majesty's Stationery Office, 1981.

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Table 1

TABLE 1. Acceptable presumptive evidence of immunity to measles, rubella, and mumps
============================================================================================================
Routine Persons who work in International Students at post-high
health-care travelers school educational
facilities* institutions
------------------------------------------------------------------------------------------------------------
Measles (1) documentation of (1) documented (1) documented (1) documented
adequate administration of administration of administration of
vaccination+: - 2 doses of live 2 doses of live 2 doses of live
preschool-aged measles virus measles virus measles virus
children and adults vaccine+@,or vaccine+**,or vaccine+,or
not at high risk: 1 (2) laboratory (2) laboratory (2) laboratory
dose - school-aged evidence of evidence of evidence of
children (grades K- immunity,or immunity,or immunity,or
12): 2 doses&,or (3) born before (3) born before (3) born before
(2) laboratory 1957&,or 1957,or 1957,or
evidence of (4) documentation of (4) documentation of (4) documentation of
immunity,or physician-diagnosed physician-diagnosed physician-diagnosed
(3) born before measles measles measles
1957,or
(4) documentation of
physician-diagnosed
measles
Rubella (1) documented (1) documented (1) documented (1) documented
administration of one administration of one administration of one administration of one
dose of live rubella dose of live rubella dose of live rubella dose of live rubella
virus, virus vaccine+,or virus vaccine+,or virus vaccine+,or
vaccine+,or (2) laboratory (2) laboratory (2) laboratory
(2) laboratory evidence of evidence of immunity, evidence of
evidence of immunity,or or immunity,or
immunity,or (3) born before 1957 (3) born before 1957 (3) born before 1957
(3) born before 1957 (except women of (except women of (except women of
(except women of childbearing age who childbearing age who childbearing age who
childbearing age who could become could become could become
could become pregnant++) pregnant++) pregnant++)
pregnant++)
Mumps (1) documented (1) documented (1) documented (1) documented
administration of one administration of one administration of one administration of one
dose of live mumps dose of live mumps dose of live mumps dose of live mumps
virus vaccine+,or virus vaccine+ virus vaccine+ virus vaccine+
(2) laboratory (2) laboratory (2) laboratory (2) laboratory
evidence of evidence of evidence of evidence of
immunity,or immunity,or immunity,or immunity,or
(3) born before (3) born before (3) born before (3) born before
1957,or 1957,or 1957,or 1957,or
(4) documentation of (4) documentation of (4) documentation of (4) documentation of
physician-diagnosed physician-diagnosed physician-diagnosed physician-diagnosed
mumps mumps mumps mumps
------------------------------------------------------------------------------------------------------------
* Health care workers include all persons (i. e., medical or nonmedical, paid or volunteer, full- or part-
time, student or nonstudent, with or without patient- care responsibilities) who
work in facilities that provide health care to patients (i. e., inpatient and outpatient, private and
public). Facilities that provide care exclusively for elderly patients who are at
minimal risk for measles and rubella and complications of these diseases are a possible exception.
+ The first dose should be administered on or after the first birthday; the second dose of measles-
containing vaccine should be administered no earlier than one month (i. e., minimum of 28 days) after
the first dose. Combined measles- mumps- rubella (MMR) vaccine generally should be used whenever any of
its component vaccines is indicated.
& May vary depending on current state or local requirements.
@ Health- care facilities should consider recommending a dose of MMR vaccine for unvaccinated workers
born before 1957 who are at risk for occupational exposure to measles and who do not have a history
of measles disease or laboratory evidence of measles immunity.
** Children aged 6- 11 months should receive a dose of monovalent measles vaccine (or MMR, if monovalent
vaccine is not available) before departure. Children who receive a dose of measles- containing
vaccine before their first birthdays should be revaccinated with two doses of MMR vaccine, the first
of which should be administered when the child is aged 12- 15 months (12 months if the child remains
in a high- risk area) and the second at least 28 days later.
++ Women of childbearing age are adolescent girls and premenopausal adult women. Because rubella can
occur in some persons born before 1957 and because congenital rubella and congenital rubella
syndrome can occur in the offspring of women infected with rubella virus during pregnancy, birth
before 1957 is not acceptable evidence of rubella immunity for women who could become pregnant.
============================================================================================================